chr8-24394146-T-C

Position:

• chr8-24394146-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014479.3(ADAMDEC1):​c.362T>C​(p.Met121Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,607,606 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.026 (164 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (176 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense, splice_region
• Scores: Splicing: ADA: 0.00001287
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.361

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00237903).
• BP6: Variant 8-24394146-T-C is Benign according to our data. Variant chr8-24394146-T-C is described in ClinVar as [Benign]. Clinvar id is 781121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMDEC1	NM_014479.3	c.362T>C	p.Met121Thr	missense_variant, splice_region_variant	4/14	ENST00000256412.8	NP_055294.1
ADAM7-AS1	NR_125808.1	n.80-6155A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMDEC1	ENST00000256412.8	c.362T>C	p.Met121Thr	missense_variant, splice_region_variant	4/14	1	NM_014479.3	ENSP00000256412	P1
ADAM7-AS1	ENST00000519689.1	n.185-6155A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3914 AN: 152140 Hom.: 162 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00682 AC: 1710 AN: 250712 Hom.: 79 AF XY: 0.00505 AC XY: 684 AN XY: 135496

Gnomad AFR exome AF: 0.0946

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00393

GnomAD4 exome AF: 0.00270 AC: 3928 AN: 1455348 Hom.: 176 Cov.: 29 AF XY: 0.00226 AC XY: 1634 AN XY: 724360

Gnomad4 AFR exome AF: 0.0955

Gnomad4 AMR exome AF: 0.00407

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000314

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000139

Gnomad4 OTH exome AF: 0.00612

GnomAD4 genome AF: 0.0258 AC: 3932 AN: 152258 Hom.: 164 Cov.: 32 AF XY: 0.0249 AC XY: 1855 AN XY: 74446

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00444 Hom.: 71

Bravo AF: 0.0293

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0887 AC: 391

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00825 AC: 1001

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000357

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.2
DANN	Benign	0.50
DEOGEN2	Benign	0.0079	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.0080
Sift	Benign	0.17	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0040	B;.
Vest4		0.19
MVP		0.15
MPC		0.062
ClinPred		0.0035	T
GERP RS		-0.31
Varity_R		0.089
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0020
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: rs7007084; hg19: chr8-24251659;