Genetic Variant KIAA1549:c.187+27403G>T (chr7-138953680-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001164665.2(KIAA1549):c.187+27403G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00991 in 152,188 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0099 ( 16 hom., cov: 33)

Consequence

KIAA1549
NM_001164665.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00991 (1508/152188) while in subpopulation NFE AF = 0.0152 (1036/68000). AF 95% confidence interval is 0.0145. There are 16 homozygotes in GnomAd4. There are 661 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2 link	c.187+27403G>T		intron_variant	Intron 1 of 19	ENST00000422774.2	NP_001158137.1	Q9HCM3-1
KIAA1549	NM_020910.3 link	c.187+27403G>T		intron_variant	Intron 1 of 19		NP_065961.2	Q9HCM3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2 link	c.187+27403G>T		intron_variant	Intron 1 of 19	1	NM_001164665.2	ENSP00000416040.2		Q9HCM3-1
KIAA1549	ENST00000440172.5 link	c.187+27403G>T		intron_variant	Intron 1 of 19	1		ENSP00000406661.1		Q9HCM3-2

Frequencies

GnomAD3 genomes

AF:

0.00992

AC:

1508

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00307

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00312

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0148

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00991

AC:

1508

AN:

152188

Hom.:

Cov.:

AF XY:

0.00888

AC XY:

661

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41528

American (AMR)

AF:

0.0141

AC:

215

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00312

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1036

AN:

68000

Other (OTH)

AF:

0.0147

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

152

227

303

379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00175

Hom.:

Bravo

AF:

0.0112

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.7

(source)

DANN

Benign

0.63

PhyloP100

-0.042

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over