rs2242669

Variant names:

• chr19-50910534-G-A
• rs2242669
• NM_004917.5:c.61+144C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50910534-G-A
• chr19-50910534-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004917.5(KLK4):​c.61+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 775,154 control chromosomes in the GnomAD database, including 13,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3518 hom., cov: 31)
  • Exomes 𝑓: 0.17 (10017 hom.)
• Consequence: KLK4 NM_004917.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.47
• Publications: 5 publications found

Genes affected

KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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 a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

KLK4 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 2A1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-50910534-G-A is Benign according to our data. Variant chr19-50910534-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK4	NM_004917.5	c.61+144C>T		intron_variant	Intron 2 of 5	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.-237+144C>T		intron_variant	Intron 1 of 4		NP_001289890.1
KLK4	NR_126566.2	n.61+144C>T		intron_variant	Intron 1 of 4
KLK4	XM_011527545.4	c.61+144C>T		intron_variant	Intron 1 of 3		XP_011525847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.61+144C>T		intron_variant	Intron 2 of 5	1	NM_004917.5	ENSP00000326159.1
KLK4	ENST00000598305.5	n.-218+144C>T		intron_variant	Intron 1 of 4	1		ENSP00000469963.1
KLK4	ENST00000602148.1	n.61+144C>T		intron_variant	Intron 1 of 4	1		ENSP00000472091.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31520 AN: 151908 Hom.: 3505 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.174 AC: 108360 AN: 623128 Hom.: 10017 AF XY: 0.174 AC XY: 57883 AN XY: 331828

African (AFR) AF: 0.296 AC: 4969 AN: 16788

American (AMR) AF: 0.121 AC: 4181 AN: 34542

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 2896 AN: 20156

East Asian (EAS) AF: 0.170 AC: 5429 AN: 32020

South Asian (SAS) AF: 0.186 AC: 11761 AN: 63210

European-Finnish (FIN) AF: 0.191 AC: 8540 AN: 44684

Middle Eastern (MID) AF: 0.217 AC: 887 AN: 4094

European-Non Finnish (NFE) AF: 0.169 AC: 63442 AN: 375134

Other (OTH) AF: 0.192 AC: 6255 AN: 32500

GnomAD4 genome AF: 0.208 AC: 31567 AN: 152026 Hom.: 3518 Cov.: 31 AF XY: 0.206 AC XY: 15297 AN XY: 74284

African (AFR) AF: 0.297 AC: 12285 AN: 41418

American (AMR) AF: 0.158 AC: 2421 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3472

East Asian (EAS) AF: 0.174 AC: 898 AN: 5164

South Asian (SAS) AF: 0.177 AC: 852 AN: 4812

European-Finnish (FIN) AF: 0.188 AC: 1989 AN: 10580

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11888 AN: 67984

Other (OTH) AF: 0.214 AC: 450 AN: 2106

Alfa AF: 0.186 Hom.: 566

Bravo AF: 0.210

Asia WGS AF: 0.191 AC: 667 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.45
PhyloP100		1.5
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: rs2242669; hg19: chr19-51413790; COSMIC: COSV60676515; COSMIC: COSV60676515;