7-138917686-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164665.2(KIAA1549):c.1940C>G(p.Ser647Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 1,609,428 control chromosomes in the GnomAD database, including 3,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 286 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3577 hom. )

Consequence

KIAA1549
NM_001164665.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.937

Publications

14 publications found

Variant links:

Genes affected

KIAA1549 (HGNC:22219): (KIAA1549) The protein encoded by this gene belongs to the UPF0606 family. This gene has been found to be fused to the BRAF oncogene in many cases of pilocytic astrocytoma. The fusion results from 2Mb tandem duplications at 7q34. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

KIAA1549 Gene-Disease associations (from GenCC):

retinitis pigmentosa 86
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

KIAA1549 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020231009).

BP6

Variant 7-138917686-G-C is Benign according to our data. Variant chr7-138917686-G-C is described in ClinVar as Benign. ClinVar VariationId is 1167366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2 link	c.1940C>G	p.Ser647Cys	missense_variant	Exon 2 of 20	ENST00000422774.2	NP_001158137.1	Q9HCM3-1
KIAA1549	NM_020910.3 link	c.1940C>G	p.Ser647Cys	missense_variant	Exon 2 of 20		NP_065961.2	Q9HCM3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2 link	c.1940C>G	p.Ser647Cys	missense_variant	Exon 2 of 20	1	NM_001164665.2	ENSP00000416040.2		Q9HCM3-1
KIAA1549	ENST00000440172.5 link	c.1940C>G	p.Ser647Cys	missense_variant	Exon 2 of 20	1		ENSP00000406661.1		Q9HCM3-2

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

8379

AN:

152128

Hom.:

286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0689

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0631

AC:

15129

AN:

239650

AF XY:

0.0680

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.0329

Gnomad ASJ exome

AF:

0.0778

Gnomad EAS exome

AF:

0.000347

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0708

GnomAD4 exome

AF:

0.0663

AC:

96563

AN:

1457182

Hom.:

3577

Cov.:

AF XY:

0.0685

AC XY:

49613

AN XY:

724218

show subpopulations

African (AFR)

AF:

0.0352

AC:

1173

AN:

33370

American (AMR)

AF:

0.0336

AC:

1479

AN:

43988

Ashkenazi Jewish (ASJ)

AF:

0.0749

AC:

1949

AN:

26026

East Asian (EAS)

AF:

0.000278

AC:

AN:

39608

South Asian (SAS)

AF:

0.126

AC:

10790

AN:

85496

European-Finnish (FIN)

AF:

0.0470

AC:

2498

AN:

53204

Middle Eastern (MID)

AF:

0.102

AC:

586

AN:

5760

European-Non Finnish (NFE)

AF:

0.0668

AC:

74143

AN:

1109506

Other (OTH)

AF:

0.0653

AC:

3934

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5131

10261

15392

20522

25653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2750

5500

8250

11000

13750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0550

AC:

8378

AN:

152246

Hom.:

286

Cov.:

AF XY:

0.0552

AC XY:

4109

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0356

AC:

1478

AN:

41542

American (AMR)

AF:

0.0408

AC:

624

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0723

AC:

251

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5170

South Asian (SAS)

AF:

0.132

AC:

636

AN:

4820

European-Finnish (FIN)

AF:

0.0455

AC:

483

AN:

10604

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0688

AC:

4683

AN:

68022

Other (OTH)

AF:

0.0672

AC:

142

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

408

817

1225

1634

2042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0680

Hom.:

Bravo

AF:

0.0505

TwinsUK

AF:

0.0739

AC:

274

ALSPAC

AF:

0.0641

AC:

247

ESP6500AA

AF:

0.0290

AC:

114

ESP6500EA

AF:

0.0690

AC:

574

ExAC

AF:

0.0649

AC:

7838

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Retinitis pigmentosa 86

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.029

.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PhyloP100

0.94

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.031

Sift

Benign

0.059

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.99

D;D

Vest4

0.15

MPC

0.38

ClinPred

0.0072

GERP RS

1.1

Varity_R

0.054

gMVP

0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over