6-61702248-C-T

Variant names:

• chr6-61702248-C-T
• rs9294311
• NM_152688.4:c.894-4995G>A

Variant summary

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

The NM_152688.4(KHDRBS2):​c.894-4995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,642 control chromosomes in the GnomAD database, including 10,281 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 0.35 (10281 hom., cov: 31)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 0 publications found

Genes affected

KHDRBS2 (HGNC:18114): (KH RNA binding domain containing, signal transduction associated 2) Predicted to enable mRNA binding activity and poly(A) binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.894-4995G>A		intron_variant	Intron 7 of 8	ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.894-4995G>A		intron_variant	Intron 7 of 8	1	NM_152688.4	ENSP00000281156.3
KHDRBS2	ENST00000675091.1	n.*50-4995G>A		intron_variant	Intron 8 of 9			ENSP00000502245.1
KHDRBS2	ENST00000718012.1	n.894-4995G>A		intron_variant	Intron 7 of 13			ENSP00000520654.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53552 AN: 151522 Hom.: 10277 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.353 AC: 53563 AN: 151642 Hom.: 10281 Cov.: 31 AF XY: 0.351 AC XY: 26017 AN XY: 74082

African (AFR) AF: 0.193 AC: 7983 AN: 41396

American (AMR) AF: 0.409 AC: 6214 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3464

East Asian (EAS) AF: 0.484 AC: 2473 AN: 5108

South Asian (SAS) AF: 0.322 AC: 1545 AN: 4804

European-Finnish (FIN) AF: 0.370 AC: 3907 AN: 10548

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28804 AN: 67818

Other (OTH) AF: 0.390 AC: 818 AN: 2100

Alfa AF: 0.237 Hom.: 608

Bravo AF: 0.352

Asia WGS AF: 0.335 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.43
PhyloP100		-0.69
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: rs9294311; hg19: chr6-62412153;