6-61697162-G-T

Variant names:

• chr6-61697162-G-T
• rs1555167
• NM_152688.4:c.952+33C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152688.4(KHDRBS2):​c.952+33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,394,510 control chromosomes in the GnomAD database, including 119,627 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 (10300 hom., cov: 31)
  • Exomes 𝑓: 0.42 (109327 hom.)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.952+33C>A		intron_variant	Intron 8 of 8	ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.952+33C>A		intron_variant	Intron 8 of 8	1	NM_152688.4	ENSP00000281156.3
KHDRBS2	ENST00000675091.1	n.*108+33C>A		intron_variant	Intron 9 of 9			ENSP00000502245.1
KHDRBS2	ENST00000718012.1	n.952+33C>A		intron_variant	Intron 8 of 13			ENSP00000520654.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53628 AN: 151774 Hom.: 10296 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.400 AC: 100186 AN: 250308 AF XY: 0.398

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.490

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.415 AC: 516079 AN: 1242618 Hom.: 109327 Cov.: 18 AF XY: 0.413 AC XY: 260243 AN XY: 630172

African (AFR) AF: 0.179 AC: 5217 AN: 29112

American (AMR) AF: 0.469 AC: 20825 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 8778 AN: 24752

East Asian (EAS) AF: 0.501 AC: 19335 AN: 38600

South Asian (SAS) AF: 0.330 AC: 26990 AN: 81900

European-Finnish (FIN) AF: 0.382 AC: 20282 AN: 53064

Middle Eastern (MID) AF: 0.446 AC: 2396 AN: 5372

European-Non Finnish (NFE) AF: 0.429 AC: 391098 AN: 912338

Other (OTH) AF: 0.398 AC: 21158 AN: 53110

GnomAD4 genome AF: 0.353 AC: 53639 AN: 151892 Hom.: 10300 Cov.: 31 AF XY: 0.351 AC XY: 26052 AN XY: 74208

African (AFR) AF: 0.193 AC: 8011 AN: 41466

American (AMR) AF: 0.409 AC: 6234 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2489 AN: 5132

South Asian (SAS) AF: 0.321 AC: 1546 AN: 4812

European-Finnish (FIN) AF: 0.371 AC: 3906 AN: 10534

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28813 AN: 67922

Other (OTH) AF: 0.387 AC: 816 AN: 2106

Alfa AF: 0.315 Hom.: 1707

Bravo AF: 0.352

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		1.9
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: rs1555167; hg19: chr6-62407067; COSMIC: COSV55436851;