7-138847463-G-A

Variant names:

• chr7-138847463-G-A
• rs6467813
• NM_001164665.2:c.5295-2989C>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.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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2	c.5295-2989C>T		intron_variant	Intron 17 of 19	ENST00000422774.2	NP_001158137.1
KIAA1549	NM_020910.3	c.5295-2989C>T		intron_variant	Intron 17 of 19		NP_065961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2	c.5295-2989C>T		intron_variant	Intron 17 of 19	1	NM_001164665.2	ENSP00000416040.2
KIAA1549	ENST00000440172.5	c.5295-2989C>T		intron_variant	Intron 17 of 19	1		ENSP00000406661.1

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

African (AFR) AF: 0.641 AC: 26592 AN: 41468

American (AMR) AF: 0.660 AC: 10096 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4743 AN: 5180

South Asian (SAS) AF: 0.682 AC: 3291 AN: 4822

European-Finnish (FIN) AF: 0.652 AC: 6895 AN: 10576

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47039 AN: 67994

Other (OTH) AF: 0.727 AC: 1536 AN: 2112

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
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6467813; hg19: chr7-138532208;