rs1204116

chr6-61694191-C-Achr6-61694191-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152688.4(KHDRBS2):c.952+3004G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,080 control chromosomes in the GnomAD database, including 3,546 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 0.20 (3546 hom., cov: 33)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS2	NM_152688.4	c.952+3004G>T		intron_variant		ENST00000281156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.952+3004G>T		intron_variant		1	NM_152688.4	P1
KHDRBS2	ENST00000675091.1	c.*108+3004G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30102 AN: 151962 Hom.: 3541 Cov.: 33

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.198 AC: 30116 AN: 152080 Hom.: 3546 Cov.: 33 AF XY: 0.206 AC XY: 15296 AN XY: 74312

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.193

Alfa AF: 0.213 Hom.: 1772

Bravo AF: 0.178

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.056
Dann	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs1204116; hg19: chr6-62404096;