Variant 12-8138285-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_016184.4(CLEC4A):c.712T>C(p.Ter238ArgextTer6) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,614,160 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00071 ( 7 hom. )

Consequence

CLEC4A
NM_016184.4 stop_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.892

Variant links:

Genes affected

CLEC4A (HGNC:13257): (C-type lectin domain family 4 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

CLEC4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Stoplost variant in NM_016184.4 Downstream stopcodon found after 324 codons.

BP6

Variant 12-8138285-T-C is Benign according to our data. Variant chr12-8138285-T-C is described in ClinVar as [Benign]. Clinvar id is 732592.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLEC4A	NM_016184.4 linkuse as main transcript	c.712T>C	p.Ter238ArgextTer6	stop_lost	6/6	ENST00000229332.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLEC4A	ENST00000229332.12 linkuse as main transcript	c.712T>C	p.Ter238ArgextTer6	stop_lost	6/6	1	NM_016184.4	P1	Q9UMR7-1
CLEC4A	ENST00000352620.9 linkuse as main transcript	c.613T>C	p.Ter205ArgextTer?	stop_lost	5/5	1			Q9UMR7-2
CLEC4A	ENST00000360500.5 linkuse as main transcript	c.595T>C	p.Ter199ArgextTer?	stop_lost	5/5	5			Q9UMR7-3
CLEC4A	ENST00000345999.9 linkuse as main transcript	c.496T>C	p.Ter166ArgextTer6	stop_lost	4/4	5			Q9UMR7-4

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

718

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00140

AC:

351

AN:

251378

Hom.:

AF XY:

0.00110

AC XY:

150

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000706

AC:

1032

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

494

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00473

AC:

720

AN:

152306

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00517

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00180

AC:

219

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.81

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.37

MutationTaster

Benign

1.0

N;N;N;N

Vest4

0.39

GERP RS

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over