rs6455128

Variant names:

• chr6-61987841-A-C
• rs6455128
• NM_152688.4:c.337-9629T>G

Variant summary

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

The NM_152688.4(KHDRBS2):​c.337-9629T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,076 control chromosomes in the GnomAD database, including 48,297 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 0.79 (48297 hom., cov: 32)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• Publications: 23 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.337-9629T>G		intron_variant	Intron 3 of 8	ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.337-9629T>G		intron_variant	Intron 3 of 8	1	NM_152688.4	ENSP00000281156.3
KHDRBS2	ENST00000675091.1	n.337-9629T>G		intron_variant	Intron 3 of 9			ENSP00000502245.1
KHDRBS2	ENST00000718012.1	n.337-9629T>G		intron_variant	Intron 3 of 13			ENSP00000520654.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120690 AN: 151958 Hom.: 48257 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.794 AC: 120780 AN: 152076 Hom.: 48297 Cov.: 32 AF XY: 0.797 AC XY: 59280 AN XY: 74348

African (AFR) AF: 0.704 AC: 29190 AN: 41456

American (AMR) AF: 0.831 AC: 12675 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2650 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4332 AN: 5146

South Asian (SAS) AF: 0.746 AC: 3597 AN: 4824

European-Finnish (FIN) AF: 0.908 AC: 9633 AN: 10610

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56046 AN: 67994

Other (OTH) AF: 0.786 AC: 1661 AN: 2114

Alfa AF: 0.809 Hom.: 182069

Bravo AF: 0.787

Asia WGS AF: 0.772 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-0.79
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: rs6455128; hg19: chr6-62697746;