rs6467813

Positions:

• chr7-138847463-G-A
• chr7-138847463-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164665.2(KIAA1549):​c.5295-2989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,120 control chromosomes in the GnomAD database, including 35,654 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 0.68 (35654 hom., cov: 32)
• Consequence: KIAA1549 NM_001164665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1549	NM_001164665.2	c.5295-2989C>T		intron_variant		ENST00000422774.2
KIAA1549	NM_020910.3	c.5295-2989C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1549	ENST00000422774.2	c.5295-2989C>T		intron_variant		1	NM_001164665.2	A2
KIAA1549	ENST00000440172.5	c.5295-2989C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103643 AN: 152002 Hom.: 35609 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.682 AC: 103740 AN: 152120 Hom.: 35654 Cov.: 32 AF XY: 0.681 AC XY: 50668 AN XY: 74376

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.727

Alfa AF: 0.672 Hom.: 4272

Bravo AF: 0.687

Asia WGS AF: 0.808 AC: 2809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6467813; hg19: chr7-138532208; COSMIC: COSV99649581;