rs16873582

Variant names:

• chr7-138911255-G-A
• rs16873582
• NM_001164665.2:c.3036C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001164665.2(KIAA1549):​c.3036C>T​(p.Ser1012Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 1,602,556 control chromosomes in the GnomAD database, including 4,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (542 hom., cov: 33)
  • Exomes 𝑓: 0.074 (4307 hom.)
• Consequence: KIAA1549 NM_001164665.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.951
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-138911255-G-A is Benign according to our data. Variant chr7-138911255-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.951 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2	c.3036C>T	p.Ser1012Ser	synonymous_variant	Exon 4 of 20	ENST00000422774.2	NP_001158137.1
KIAA1549	NM_020910.3	c.3036C>T	p.Ser1012Ser	synonymous_variant	Exon 4 of 20		NP_065961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2	c.3036C>T	p.Ser1012Ser	synonymous_variant	Exon 4 of 20	1	NM_001164665.2	ENSP00000416040.2
KIAA1549	ENST00000440172.5	c.3036C>T	p.Ser1012Ser	synonymous_variant	Exon 4 of 20	1		ENSP00000406661.1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12709 AN: 152130 Hom.: 541 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0851

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0799

GnomAD2 exomes AF: 0.0670 AC: 15638 AN: 233480 AF XY: 0.0674

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0779

Gnomad EAS exome AF: 0.0553

Gnomad FIN exome AF: 0.0425

Gnomad NFE exome AF: 0.0738

Gnomad OTH exome AF: 0.0677

GnomAD4 exome AF: 0.0741 AC: 107534 AN: 1450308 Hom.: 4307 Cov.: 31 AF XY: 0.0738 AC XY: 53140 AN XY: 720358

African (AFR) AF: 0.126 AC: 4183 AN: 33262

American (AMR) AF: 0.0373 AC: 1624 AN: 43538

Ashkenazi Jewish (ASJ) AF: 0.0754 AC: 1951 AN: 25868

East Asian (EAS) AF: 0.0576 AC: 2273 AN: 39472

South Asian (SAS) AF: 0.0711 AC: 5965 AN: 83908

European-Finnish (FIN) AF: 0.0445 AC: 2353 AN: 52894

Middle Eastern (MID) AF: 0.0945 AC: 544 AN: 5754

European-Non Finnish (NFE) AF: 0.0761 AC: 84112 AN: 1105596

Other (OTH) AF: 0.0755 AC: 4529 AN: 60016

GnomAD4 genome AF: 0.0836 AC: 12721 AN: 152248 Hom.: 542 Cov.: 33 AF XY: 0.0818 AC XY: 6091 AN XY: 74446

African (AFR) AF: 0.124 AC: 5149 AN: 41546

American (AMR) AF: 0.0532 AC: 814 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0851 AC: 295 AN: 3468

East Asian (EAS) AF: 0.0571 AC: 296 AN: 5184

South Asian (SAS) AF: 0.0714 AC: 345 AN: 4830

European-Finnish (FIN) AF: 0.0438 AC: 464 AN: 10596

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5137 AN: 68010

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0764 Hom.: 1020

Bravo AF: 0.0845

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

- -

Retinal dystrophy Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.95
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs16873582; hg19: chr7-138596001; COSMIC: COSV54308659;