rs1701946

Variant names:

• chr19-51000268-T-A
• rs1701946
• NM_007196.4:c.231-10A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51000268-T-A
• chr19-51000268-T-C
• chr19-51000268-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007196.4(KLK8):​c.231-10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLK8 NM_007196.4 intron
• Scores: Splicing: ADA: 0.00001423
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 13 publications found

Genes affected

KLK8 (HGNC:6369): (kallikrein related peptidase 8) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in tandem in a gene cluster on chromosome 19. The encoded protein may be involved in proteolytic cascade in the skin and may serve as a biomarker for ovarian cancer. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ENSG00000267879 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK8	NM_007196.4	c.231-10A>T		intron_variant	Intron 3 of 5	ENST00000695909.1	NP_009127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK8	ENST00000695909.1	c.231-10A>T		intron_variant	Intron 3 of 5		NM_007196.4	ENSP00000512260.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1415684 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 696356

African (AFR) AF: 0.00 AC: 0 AN: 32764

American (AMR) AF: 0.00 AC: 0 AN: 42922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23606

East Asian (EAS) AF: 0.00 AC: 0 AN: 39012

South Asian (SAS) AF: 0.00 AC: 0 AN: 79710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083216

Other (OTH) AF: 0.00 AC: 0 AN: 58364

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 7174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.77
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0020
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: rs1701946; hg19: chr19-51503524;