rs10954631

Variant names:

• chr7-138854880-G-A
• rs10954631
• NM_001164665.2:c.5248-2611C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164665.2(KIAA1549):​c.5248-2611C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,070 control chromosomes in the GnomAD database, including 12,049 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 0.27 (12049 hom., cov: 32)
• Consequence: KIAA1549 NM_001164665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2	c.5248-2611C>T		intron_variant	Intron 16 of 19	ENST00000422774.2	NP_001158137.1
KIAA1549	NM_020910.3	c.5248-2611C>T		intron_variant	Intron 16 of 19		NP_065961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2	c.5248-2611C>T		intron_variant	Intron 16 of 19	1	NM_001164665.2	ENSP00000416040.2
KIAA1549	ENST00000440172.5	c.5248-2611C>T		intron_variant	Intron 16 of 19	1		ENSP00000406661.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41160 AN: 151952 Hom.: 11998 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.271 AC: 41266 AN: 152070 Hom.: 12049 Cov.: 32 AF XY: 0.265 AC XY: 19737 AN XY: 74358

African (AFR) AF: 0.737 AC: 30568 AN: 41458

American (AMR) AF: 0.153 AC: 2338 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3470

East Asian (EAS) AF: 0.107 AC: 555 AN: 5168

South Asian (SAS) AF: 0.156 AC: 754 AN: 4818

European-Finnish (FIN) AF: 0.0650 AC: 689 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5080 AN: 67968

Other (OTH) AF: 0.247 AC: 523 AN: 2114

Alfa AF: 0.142 Hom.: 7176

Bravo AF: 0.298

Asia WGS AF: 0.190 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.72
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10954631; hg19: chr7-138539626;