rs2075755

Positions:

• chr19-6422877-T-C
• chr19-6422877-T-G

Variant summary

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

The NM_001366299.1(KHSRP):​c.250-441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,910 control chromosomes in the GnomAD database, including 14,525 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 0.43 (14525 hom., cov: 31)
• Consequence: KHSRP NM_001366299.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606

Genes affected

KHSRP (HGNC:6316): (KH-type splicing regulatory protein) The KHSRP gene encodes a multifunctional RNA-binding protein implicated in a variety of cellular processes, including transcription, alternative pre-mRNA splicing, and mRNA localization (Min et al., 1997 [PubMed 9136930]; Gherzi et al., 2004 [PubMed 15175153]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHSRP	NM_001366299.1	c.250-441A>G		intron_variant		ENST00000600480.2	NP_001353228.1
KHSRP	NM_001366300.1	c.250-441A>G		intron_variant			NP_001353229.1
KHSRP	NM_003685.3	c.250-441A>G		intron_variant			NP_003676.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHSRP	ENST00000600480.2	c.250-441A>G		intron_variant		2	NM_001366299.1	ENSP00000471146	A2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64857 AN: 151790 Hom.: 14494 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.427 AC: 64937 AN: 151910 Hom.: 14525 Cov.: 31 AF XY: 0.428 AC XY: 31800 AN XY: 74240

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.448

Alfa AF: 0.384 Hom.: 18386

Bravo AF: 0.457

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.69

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: rs2075755; hg19: chr19-6422888;