rs10484621

Variant names:

• chr6-61976913-G-A
• rs10484621
• NM_152688.4:c.483+1153C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152688.4(KHDRBS2):​c.483+1153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,232 control chromosomes in the GnomAD database, including 30 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 0.016 (30 hom., cov: 32)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0156 (2379/152232) while in subpopulation NFE AF = 0.0264 (1795/68010). AF 95% confidence interval is 0.0254. There are 30 homozygotes in GnomAd4. There are 1054 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.483+1153C>T		intron_variant	Intron 4 of 8	ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.483+1153C>T		intron_variant	Intron 4 of 8	1	NM_152688.4	ENSP00000281156.3
KHDRBS2	ENST00000675091.1	n.483+1153C>T		intron_variant	Intron 4 of 9			ENSP00000502245.1
KHDRBS2	ENST00000718012.1	n.483+1153C>T		intron_variant	Intron 4 of 13			ENSP00000520654.1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2378 AN: 152114 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0156 AC: 2379 AN: 152232 Hom.: 30 Cov.: 32 AF XY: 0.0142 AC XY: 1054 AN XY: 74426

African (AFR) AF: 0.00469 AC: 195 AN: 41546

American (AMR) AF: 0.0109 AC: 167 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4832

European-Finnish (FIN) AF: 0.00952 AC: 101 AN: 10614

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0264 AC: 1795 AN: 68010

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.0228 Hom.: 67

Bravo AF: 0.0150

Asia WGS AF: 0.00145 AC: 5 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism

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: rs10484621; hg19: chr6-62686818;