19-50977620-G-A

Variant names:

• chr19-50977620-G-A
• rs17855561
• NM_005046.4:c.678C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005046.4(KLK7):​c.678C>T​(p.Cys226Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,613,418 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (4 hom.)
• Consequence: KLK7 NM_005046.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 19-50977620-G-A is Benign according to our data. Variant chr19-50977620-G-A is described in ClinVar as Benign. ClinVar VariationId is 784839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.7 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005046.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK7	NM_005046.4	MANE Select	c.678C>T	p.Cys226Cys	synonymous	Exon 6 of 6	NP_005037.1
	KLK7	NM_139277.2		c.678C>T	p.Cys226Cys	synonymous	Exon 6 of 6	NP_644806.1
	KLK7	NM_001243126.1		c.657C>T	p.Cys219Cys	synonymous	Exon 5 of 5	NP_001230055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK7	ENST00000595820.6	TSL:1 MANE Select	c.678C>T	p.Cys226Cys	synonymous	Exon 6 of 6	ENSP00000470538.1
	KLK7	ENST00000597707.5	TSL:1	c.462C>T	p.Cys154Cys	synonymous	Exon 5 of 5	ENSP00000469950.1
	KLK7	ENST00000391807.5	TSL:5	c.678C>T	p.Cys226Cys	synonymous	Exon 6 of 6	ENSP00000375683.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 151860 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00121 AC: 305 AN: 251352 AF XY: 0.000787

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00853

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000253 AC: 370 AN: 1461558 Hom.: 4 Cov.: 32 AF XY: 0.000204 AC XY: 148 AN XY: 727050

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00774 AC: 346 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111936

Other (OTH) AF: 0.000132 AC: 8 AN: 60378

GnomAD4 genome AF: 0.000204 AC: 31 AN: 151860 Hom.: 1 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74160

African (AFR) AF: 0.0000726 AC: 3 AN: 41326

American (AMR) AF: 0.00177 AC: 27 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000232 Hom.: 0

Bravo AF: 0.000680

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.30
DANN	Benign	0.53
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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: rs17855561; hg19: chr19-51480876; COSMIC: COSV58344277; COSMIC: COSV58344277;