rs7829965

Variant names:

• chr8-24349925-G-A
• rs7829965
• NM_014265.6:c.2052G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-24349925-G-A
• chr8-24349925-G-C

Variant summary

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

The NM_014265.6(ADAM28):​c.2052G>A​(p.Met684Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,246 control chromosomes in the GnomAD database, including 1,980 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 0.054 (316 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1664 hom.)
• Consequence: ADAM28 NM_014265.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 18 publications found

Genes affected

ADAM28 (HGNC:206): (ADAM metallopeptidase domain 28) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is a lymphocyte-expressed ADAM protein. This gene is present in a gene cluster with other members of the ADAM family on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

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=0.0014255345).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM28	NM_014265.6	MANE Select	c.2052G>A	p.Met684Ile	missense	Exon 19 of 23	NP_055080.2	Q9UKQ2-1
	ADAM28	NM_001304351.2		c.2052G>A	p.Met684Ile	missense	Exon 19 of 22	NP_001291280.1
	ADAM28	NR_130710.2		n.2199G>A		non_coding_transcript_exon	Exon 19 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM28	ENST00000265769.9	TSL:1 MANE Select	c.2052G>A	p.Met684Ile	missense	Exon 19 of 23	ENSP00000265769.4	Q9UKQ2-1
	ADAM28	ENST00000699027.1		c.2052G>A	p.Met684Ile	missense	Exon 19 of 24	ENSP00000514095.1	A0A8V8TMM6
	ADAM28	ENST00000904759.1		c.2052G>A	p.Met684Ile	missense	Exon 19 of 23	ENSP00000574818.1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8121 AN: 151972 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0436

GnomAD2 exomes AF: 0.0466 AC: 11704 AN: 251202 AF XY: 0.0470

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0333

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.0319

Gnomad NFE exome AF: 0.0261

Gnomad OTH exome AF: 0.0318

GnomAD4 exome AF: 0.0375 AC: 54748 AN: 1461156 Hom.: 1664 Cov.: 30 AF XY: 0.0388 AC XY: 28226 AN XY: 726856

African (AFR) AF: 0.106 AC: 3556 AN: 33436

American (AMR) AF: 0.0333 AC: 1487 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0175 AC: 457 AN: 26112

East Asian (EAS) AF: 0.124 AC: 4909 AN: 39622

South Asian (SAS) AF: 0.0944 AC: 8135 AN: 86160

European-Finnish (FIN) AF: 0.0314 AC: 1677 AN: 53396

Middle Eastern (MID) AF: 0.0274 AC: 158 AN: 5764

European-Non Finnish (NFE) AF: 0.0288 AC: 32031 AN: 1111604

Other (OTH) AF: 0.0387 AC: 2338 AN: 60354

GnomAD4 genome AF: 0.0536 AC: 8151 AN: 152090 Hom.: 316 Cov.: 32 AF XY: 0.0538 AC XY: 4001 AN XY: 74324

African (AFR) AF: 0.101 AC: 4204 AN: 41490

American (AMR) AF: 0.0332 AC: 507 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.103 AC: 532 AN: 5152

South Asian (SAS) AF: 0.0963 AC: 463 AN: 4810

European-Finnish (FIN) AF: 0.0321 AC: 340 AN: 10584

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0284 AC: 1933 AN: 68000

Other (OTH) AF: 0.0446 AC: 94 AN: 2108

Alfa AF: 0.0366 Hom.: 718

Bravo AF: 0.0548

TwinsUK AF: 0.0251 AC: 93

ALSPAC AF: 0.0306 AC: 118

ESP6500AA AF: 0.101 AC: 443

ESP6500EA AF: 0.0276 AC: 237

ExAC AF: 0.0490 AC: 5945

Asia WGS AF: 0.117 AC: 404 AN: 3478

EpiCase AF: 0.0237

EpiControl AF: 0.0237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.3
DANN	Benign	0.53
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.8	N
PhyloP100		0.021
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.42		Loss of sheet (P = 7e-04)
MPC		0.040
ClinPred		0.0023	T
GERP RS		-0.58
Varity_R		0.032
gMVP		0.20
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs7829965; hg19: chr8-24207438; COSMIC: COSV56101013; COSMIC: COSV56101013;