rs16873582

chr7-138911255-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001164665.2(KIAA1549):c.3036C>T(p.Ser1012=) 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:2
• Conservation: PhyloP100: -0.951

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
KIAA1549	NM_001164665.2	c.3036C>T	p.Ser1012=	synonymous_variant	4/20	ENST00000422774.2
KIAA1549	NM_020910.3	c.3036C>T	p.Ser1012=	synonymous_variant	4/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1549	ENST00000422774.2	c.3036C>T	p.Ser1012=	synonymous_variant	4/20	1	NM_001164665.2	A2
KIAA1549	ENST00000440172.5	c.3036C>T	p.Ser1012=	synonymous_variant	4/20	1		P4

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

GnomAD3 exomes AF: 0.0670 AC: 15638 AN: 233480 Hom.: 600 AF XY: 0.0674 AC XY: 8490 AN XY: 126018

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 SAS exome AF: 0.0705

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

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0373

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.0576

Gnomad4 SAS exome AF: 0.0711

Gnomad4 FIN exome AF: 0.0445

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.0755

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0851

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0760 Hom.: 756

Bravo AF: 0.0845

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Retinal dystrophy Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.3
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

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