rs2075755

Variant names:

• chr19-6422877-T-C
• rs2075755
• NM_001366299.1:c.250-441A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KHSRP	NM_001366299.1	c.250-441A>G		intron_variant	Intron 1 of 18	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3	c.250-441A>G		intron_variant	Intron 1 of 19		NP_003676.2
KHSRP	NM_001366300.1	c.250-441A>G		intron_variant	Intron 1 of 19		NP_001353229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KHSRP	ENST00000600480.2	c.250-441A>G		intron_variant	Intron 1 of 18	2	NM_001366299.1	ENSP00000471146.2

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

African (AFR) AF: 0.528 AC: 21876 AN: 41406

American (AMR) AF: 0.549 AC: 8369 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1865 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2468 AN: 5182

South Asian (SAS) AF: 0.301 AC: 1448 AN: 4814

European-Finnish (FIN) AF: 0.304 AC: 3206 AN: 10544

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24148 AN: 67934

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.390 Hom.: 44197

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
PhyloP100		-0.61
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: rs2075755; hg19: chr19-6422888;