rs1743448

Positions:

• chr6-61800405-A-G
• chr6-61800405-A-T

Variant summary

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

The NM_152688.4(KHDRBS2):​c.811-67641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,892 control chromosomes in the GnomAD database, including 32,039 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 0.64 (32039 hom., cov: 31)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHDRBS2	NM_152688.4	c.811-67641T>C		intron_variant		ENST00000281156.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.811-67641T>C		intron_variant		1	NM_152688.4	P1
KHDRBS2	ENST00000675091.1	c.811-67641T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97440 AN: 151774 Hom.: 31991 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.642 AC: 97543 AN: 151892 Hom.: 32039 Cov.: 31 AF XY: 0.644 AC XY: 47791 AN XY: 74204

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.605

Alfa AF: 0.583 Hom.: 26873

Bravo AF: 0.642

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1743448; hg19: chr6-62510310;