rs1991818

Variant names:

• chr19-50981757-C-G
• rs1991818
• NM_005046.4:c.221+10G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-50981757-C-G
• chr19-50981757-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005046.4(KLK7):​c.221+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,426 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KLK7 NM_005046.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839

Genes affected

KLK7 (HGNC:6368): (kallikrein related peptidase 7) This gene encodes a member of the kallikrein subfamily of serine proteases. These enzymes have diverse physiological functions and many kallikrein genes are biomarkers for cancer. The encoded protein has chymotrypsin-like activity and plays a role in the proteolysis of intercellular cohesive structures that precedes desquamation, the shedding of the outermost layer of the epidermis. The encoded protein may play a role in cancer invasion and metastasis, and increased expression of this gene is associated with unfavorable prognosis and progression of several types of cancer. Polymorphisms in this gene may play a role in the development of atopic dermatitis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is one of fifteen kallikrein subfamily members located in a gene cluster on chromosome 19. [provided by RefSeq, May 2011]

ENSG00000267879 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK7	NM_005046.4	c.221+10G>C		intron_variant	Intron 3 of 5	ENST00000595820.6	NP_005037.1
KLK7	NM_139277.2	c.221+10G>C		intron_variant	Intron 3 of 5		NP_644806.1
KLK7	NM_001243126.1	c.200+570G>C		intron_variant	Intron 2 of 4		NP_001230055.1
KLK7	NM_001207053.2	c.5+10G>C		intron_variant	Intron 2 of 4		NP_001193982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK7	ENST00000595820.6	c.221+10G>C		intron_variant	Intron 3 of 5	1	NM_005046.4	ENSP00000470538.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385426 Hom.: 0 Cov.: 40 AF XY: 0.00000146 AC XY: 1 AN XY: 683812

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
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: rs1991818; hg19: chr19-51485013;