8-24398876-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014479.3(ADAMDEC1):c.765A>T(p.Ile255=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,282 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (67 hom.)
• Consequence: ADAMDEC1 NM_014479.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0320

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-24398876-A-T is Benign according to our data. Variant chr8-24398876-A-T is described in ClinVar as [Benign]. Clinvar id is 781134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.032 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMDEC1	NM_014479.3	c.765A>T	p.Ile255=	splice_region_variant, synonymous_variant	9/14	ENST00000256412.8
ADAM7-AS1	NR_125808.1	n.80-10885T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMDEC1	ENST00000256412.8	c.765A>T	p.Ile255=	splice_region_variant, synonymous_variant	9/14	1	NM_014479.3	P1
ADAM7-AS1	ENST00000519689.1	n.185-10885T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2574 AN: 152174 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00445 AC: 1113 AN: 250006 Hom.: 35 AF XY: 0.00324 AC XY: 438 AN XY: 135072

Gnomad AFR exome AF: 0.0614

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00328

GnomAD4 exome AF: 0.00173 AC: 2527 AN: 1460990 Hom.: 67 Cov.: 30 AF XY: 0.00147 AC XY: 1068 AN XY: 726778

Gnomad4 AFR exome AF: 0.0621

Gnomad4 AMR exome AF: 0.00263

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00436

GnomAD4 genome AF: 0.0170 AC: 2591 AN: 152292 Hom.: 78 Cov.: 32 AF XY: 0.0163 AC XY: 1216 AN XY: 74460

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00195 Hom.: 4

Bravo AF: 0.0197

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	5.2
Dann	Benign	0.70

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

Other links and lift over

dbSNP: rs7001097; hg19: chr8-24256389;