chr8-24499305-A-C

Variant names:

• chr8-24499305-A-C
• rs13259668
• NM_003817.4:c.1912A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003817.4(ADAM7):​c.1912A>C​(p.Asn638His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,597,378 control chromosomes in the GnomAD database, including 87,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8393 hom., cov: 32)
  • Exomes 𝑓: 0.33 (79202 hom.)
• Consequence: ADAM7 NM_003817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 24 publications found

Genes affected

ADAM7 (HGNC:214): (ADAM metallopeptidase domain 7) This gene encodes a member of the ADAMs family of zinc proteases. These transmembrane proteins play roles in multiple processes including cell signaling, adhesion and migration. The encoded protein lacks protease activity and may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. Mutations in this gene may be involved in the progression of melanoma. [provided by RefSeq, Oct 2011]

ADAM7-AS2 (HGNC:56153): (ADAM7 antisense RNA 2)

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.763491E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM7	NM_003817.4	MANE Select	c.1912A>C	p.Asn638His	missense	Exon 17 of 22	NP_003808.2
	ADAM7-AS1	NR_125808.1		n.79+49235T>G		intron	N/A
	ADAM7-AS2	NR_125809.1		n.447-7145T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM7	ENST00000175238.10	TSL:1 MANE Select	c.1912A>C	p.Asn638His	missense	Exon 17 of 22	ENSP00000175238.5
	ADAM7	ENST00000520720.1	TSL:1	c.1228A>C	p.Asn410His	missense	Exon 11 of 15	ENSP00000430400.1
	ADAM7	ENST00000380789.5	TSL:5	c.1912A>C	p.Asn638His	missense	Exon 17 of 23	ENSP00000370166.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49859 AN: 151814 Hom.: 8377 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.331

GnomAD2 exomes AF: 0.345 AC: 82754 AN: 240074 AF XY: 0.344

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.327 AC: 472766 AN: 1445446 Hom.: 79202 Cov.: 31 AF XY: 0.330 AC XY: 237015 AN XY: 719016

African (AFR) AF: 0.323 AC: 10608 AN: 32812

American (AMR) AF: 0.445 AC: 18750 AN: 42106

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 11287 AN: 25838

East Asian (EAS) AF: 0.229 AC: 8919 AN: 38922

South Asian (SAS) AF: 0.414 AC: 34499 AN: 83270

European-Finnish (FIN) AF: 0.308 AC: 16294 AN: 52958

Middle Eastern (MID) AF: 0.349 AC: 2001 AN: 5726

European-Non Finnish (NFE) AF: 0.317 AC: 350487 AN: 1104068

Other (OTH) AF: 0.333 AC: 19921 AN: 59746

GnomAD4 genome AF: 0.329 AC: 49914 AN: 151932 Hom.: 8393 Cov.: 32 AF XY: 0.332 AC XY: 24613 AN XY: 74242

African (AFR) AF: 0.330 AC: 13667 AN: 41468

American (AMR) AF: 0.393 AC: 5995 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1492 AN: 3464

East Asian (EAS) AF: 0.185 AC: 960 AN: 5184

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4814

European-Finnish (FIN) AF: 0.313 AC: 3297 AN: 10540

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21617 AN: 67894

Other (OTH) AF: 0.329 AC: 694 AN: 2112

Alfa AF: 0.324 Hom.: 23209

Bravo AF: 0.333

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.304 AC: 1173

ESP6500AA AF: 0.325 AC: 1430

ESP6500EA AF: 0.333 AC: 2868

ExAC AF: 0.342 AC: 41550

Asia WGS AF: 0.315 AC: 1096 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.15
DANN	Benign	0.37
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.067	T
MetaRNN	Benign	0.000078	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.85	L
PhyloP100		-1.5
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0060
Sift	Benign	0.24	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.11
MPC		0.049
ClinPred		0.0037	T
GERP RS		-4.4
Varity_R		0.044
gMVP		0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13259668; hg19: chr8-24356818; COSMIC: COSV51539527;