8-24392304-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.55

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 -14 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_single_submitter, 1 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 GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMDEC1	NM_014479.3	c.131T>G	p.Ile44Arg	missense_variant	2/14	ENST00000256412.8
ADAM7-AS1	NR_125808.1	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	c.131T>G	p.Ile44Arg	missense_variant	2/14	1	NM_014479.3	P1
ADAM7-AS1	ENST00000519689.1	n.185-4313A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00546 AC: 831 AN: 152146 Hom.: 6 Cov.: 32

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.: 4 AF XY: 0.00117 AC XY: 157 AN XY: 134172

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.: 5 Cov.: 30 AF XY: 0.000491 AC XY: 356 AN XY: 725738

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.: 6 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74436

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.: 0

Bravo AF: 0.00631

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0186 AC: 82

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00184 AC: 223

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.39
MVP		0.63
MPC		0.098
ClinPred		0.077	T
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

Other links and lift over

dbSNP: rs35372591; hg19: chr8-24249817;