Variant 8-24392304-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014479.3(ADAMDEC1):c.131T>G(p.Ile44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,611,326 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I44T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0055 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 5 hom. )

Consequence

ADAMDEC1
NM_014479.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

ADAMDEC1 (HGNC:16299): (ADAM like decysin 1) This encoded protein is thought to be a secreted protein belonging to the disintegrin metalloproteinase family. Its expression is upregulated during dendritic cells maturation. This protein may play an important role in dendritic cell function and their interactions with germinal center T cells. [provided by RefSeq, Jul 2008]

ADAMDEC1 links:

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ADAM7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012194008).

BP6

Variant 8-24392304-T-G is Benign according to our data. Variant chr8-24392304-T-G is described in ClinVar as [Benign]. Clinvar id is 717905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00547 (833/152264) while in subpopulation AFR AF= 0.0178 (740/41568). AF 95% confidence interval is 0.0167. There are 6 homozygotes in gnomad4. There are 398 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMDEC1	NM_014479.3 linkuse as main transcript	c.131T>G	p.Ile44Arg	missense_variant	2/14	ENST00000256412.8
ADAM7-AS1	NR_125808.1 linkuse as main transcript	n.80-4313A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMDEC1	ENST00000256412.8 linkuse as main transcript	c.131T>G	p.Ile44Arg	missense_variant	2/14	1	NM_014479.3	P1	O15204-1
ADAM7-AS1	ENST00000519689.1 linkuse as main transcript	n.185-4313A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00546

AC:

831

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00147

AC:

365

AN:

248334

Hom.:

AF XY:

0.00117

AC XY:

157

AN XY:

134172

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000579

AC:

845

AN:

1459062

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

356

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.0189

Gnomad4 AMR exome

AF:

0.00147

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000720

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00547

AC:

833

AN:

152264

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

398

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.00452

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000952

Hom.:

Bravo

AF:

0.00631

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00184

AC:

223

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.57

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.98

Vest4

0.39

MVP

0.63

MPC

0.098

ClinPred

0.077

GERP RS

5.3

Varity_R

0.81

gMVP

0.90

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