rs176614

Variant names:

• chr6-62238689-C-T
• rs176614
• NM_152688.4:c.91+47169G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152688.4(KHDRBS2):​c.91+47169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.41 (2379 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.91+47169G>A		intron_variant	Intron 1 of 8	ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.91+47169G>A		intron_variant	Intron 1 of 8	1	NM_152688.4	ENSP00000281156.3
KHDRBS2	ENST00000675091.1	n.91+47169G>A		intron_variant	Intron 1 of 9			ENSP00000502245.1
KHDRBS2	ENST00000718012.1	n.91+47169G>A		intron_variant	Intron 1 of 13			ENSP00000520654.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 25191 AN: 60958 Hom.: 2375 Cov.: 0

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.508

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.413

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.413 AC: 25214 AN: 61034 Hom.: 2379 Cov.: 0 AF XY: 0.412 AC XY: 12187 AN XY: 29574

African (AFR) AF: 0.448 AC: 10690 AN: 23854

American (AMR) AF: 0.336 AC: 1841 AN: 5474

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 561 AN: 1264

East Asian (EAS) AF: 0.404 AC: 825 AN: 2042

South Asian (SAS) AF: 0.493 AC: 1272 AN: 2580

European-Finnish (FIN) AF: 0.386 AC: 1018 AN: 2640

Middle Eastern (MID) AF: 0.527 AC: 59 AN: 112

European-Non Finnish (NFE) AF: 0.386 AC: 8444 AN: 21876

Other (OTH) AF: 0.415 AC: 341 AN: 822

Alfa AF: 0.170 Hom.: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.099
PhyloP100		-0.16
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: rs176614; hg19: chr6-62948594;