Genetic Variant KIAA1549:c.*2140A>G (chr7-138835766-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001164665.2(KIAA1549):c.*2140A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 220,240 control chromosomes in the GnomAD database, including 2,556 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 0.12 ( 1382 hom., cov: 32)

Exomes 𝑓: 0.17 ( 1174 hom. )

Consequence

KIAA1549
NM_001164665.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.195

Publications

4 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 links:

TMEM213 (HGNC:27220): (transmembrane protein 213) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM213 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164665.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1549	NM_001164665.2	MANE Select	c.*2140A>G		3_prime_UTR	Exon 20 of 20	NP_001158137.1	Q9HCM3-1
	KIAA1549	NM_020910.3		c.*2140A>G		3_prime_UTR	Exon 20 of 20	NP_065961.2	Q9HCM3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA1549	ENST00000422774.2	TSL:1 MANE Select	c.*2140A>G	3_prime_UTR	Exon 20 of 20	ENSP00000416040.2	Q9HCM3-1
KIAA1549	ENST00000440172.5	TSL:1	c.*2140A>G	3_prime_UTR	Exon 20 of 20	ENSP00000406661.1	Q9HCM3-2
TMEM213	ENST00000413208.1	TSL:3	c.155-2103T>C	intron	N/A	ENSP00000401570.1	A2RRL7-4

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18175

AN:

152080

Hom.:

1384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0920

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.170

AC:

11572

AN:

68042

Hom.:

1174

Cov.:

AF XY:

0.171

AC XY:

5391

AN XY:

31556

show subpopulations

African (AFR)

AF:

0.0408

AC:

128

AN:

3134

American (AMR)

AF:

0.0963

AC:

200

AN:

2076

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

695

AN:

4310

East Asian (EAS)

AF:

0.323

AC:

3170

AN:

9804

South Asian (SAS)

AF:

0.155

AC:

AN:

586

European-Finnish (FIN)

AF:

0.140

AC:

AN:

Middle Eastern (MID)

AF:

0.150

AC:

AN:

406

European-Non Finnish (NFE)

AF:

0.153

AC:

6424

AN:

41956

Other (OTH)

AF:

0.139

AC:

796

AN:

5720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

490

979

1469

1958

2448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.119

AC:

18178

AN:

152198

Hom.:

1382

Cov.:

AF XY:

0.121

AC XY:

8984

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0386

AC:

1605

AN:

41530

American (AMR)

AF:

0.0919

AC:

1406

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

539

AN:

3470

East Asian (EAS)

AF:

0.308

AC:

1591

AN:

5170

South Asian (SAS)

AF:

0.166

AC:

797

AN:

4814

European-Finnish (FIN)

AF:

0.133

AC:

1413

AN:

10596

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.153

AC:

10408

AN:

68000

Other (OTH)

AF:

0.141

AC:

298

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

797

1593

2390

3186

3983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.133

Hom.:

593

Bravo

AF:

0.114

Asia WGS

AF:

0.212

AC:

735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

(source)

DANN

Benign

0.39

PhyloP100

0.20

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over