chr8-24392292-C-T

Variant names:

• chr8-24392292-C-T
• rs61731546
• NM_014479.3:c.119C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001145271.2(ADAMDEC1):​c.-119C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,611,016 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (4 hom.)
• Consequence: ADAMDEC1 NM_001145271.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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]

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004022926).
• BP6: Variant 8-24392292-C-T is Benign according to our data. Variant chr8-24392292-C-T is described in ClinVar as [Benign]. Clinvar id is 786556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMDEC1	NM_014479.3	c.119C>T	p.Thr40Met	missense_variant	Exon 2 of 14	ENST00000256412.8	NP_055294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMDEC1	ENST00000256412.8	c.119C>T	p.Thr40Met	missense_variant	Exon 2 of 14	1	NM_014479.3	ENSP00000256412.4

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 614 AN: 152092 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00109 AC: 270 AN: 248474 AF XY: 0.000760

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.000685

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000435 AC: 634 AN: 1458806 Hom.: 4 Cov.: 30 AF XY: 0.000378 AC XY: 274 AN XY: 725620

Gnomad4 AFR exome AF: 0.0155 AC: 516 AN: 33360

Gnomad4 AMR exome AF: 0.000743 AC: 33 AN: 44394

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26072

Gnomad4 EAS exome AF: 0.0000253 AC: 1 AN: 39556

Gnomad4 SAS exome AF: 0.0000351 AC: 3 AN: 85566

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53388

Gnomad4 NFE exome AF: 0.0000225 AC: 25 AN: 1110442

Gnomad4 Remaining exome AF: 0.000863 AC: 52 AN: 60280

GnomAD4 genome AF: 0.00405 AC: 616 AN: 152210 Hom.: 2 Cov.: 32 AF XY: 0.00419 AC XY: 312 AN XY: 74400

Gnomad4 AFR AF: 0.0141 AC: 0.0141035 AN: 0.0141035

Gnomad4 AMR AF: 0.00157 AC: 0.00157274 AN: 0.00157274

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207297 AN: 0.000207297

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000294 AC: 0.000029404 AN: 0.000029404

Gnomad4 OTH AF: 0.00142 AC: 0.00142315 AN: 0.00142315

Alfa AF: 0.00165 Hom.: 3

Bravo AF: 0.00461

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00129 AC: 157

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000179

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.7
DANN	Benign	0.64
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.052
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.011	D
Polyphen		0.023	B
Vest4		0.25
MVP		0.24
MPC		0.071
ClinPred		0.0076	T
GERP RS		2.7
Varity_R		0.030
gMVP		0.34
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs61731546; hg19: chr8-24249805; COSMIC: COSV99836125; COSMIC: COSV99836125;