chr8-24313443-C-A

Variant names:

• chr8-24313443-C-A
• rs140230044
• NM_014265.6:c.439C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014265.6(ADAM28):​c.439C>A​(p.His147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,768 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: ADAM28 NM_014265.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.105
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007144958).
• BP6: Variant 8-24313443-C-A is Benign according to our data. Variant chr8-24313443-C-A is described in ClinVar as Benign. ClinVar VariationId is 708349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

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.439C>A	p.His147Asn	missense	Exon 6 of 23	NP_055080.2	Q9UKQ2-1
	ADAM28	NM_001304351.2		c.439C>A	p.His147Asn	missense	Exon 6 of 22	NP_001291280.1
	ADAM28	NM_021777.5		c.439C>A	p.His147Asn	missense	Exon 6 of 14	NP_068547.2	Q9UKQ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM28	ENST00000265769.9	TSL:1 MANE Select	c.439C>A	p.His147Asn	missense	Exon 6 of 23	ENSP00000265769.4	Q9UKQ2-1
	ADAM28	ENST00000437154.6	TSL:1	c.439C>A	p.His147Asn	missense	Exon 6 of 14	ENSP00000393699.2	Q9UKQ2-2
	ADAM28	ENST00000699027.1		c.439C>A	p.His147Asn	missense	Exon 6 of 24	ENSP00000514095.1	A0A8V8TMM6

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 296 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00273

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00203 AC: 509 AN: 250966 AF XY: 0.00207

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00356

Gnomad NFE exome AF: 0.00230

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00231 AC: 3375 AN: 1461498 Hom.: 12 Cov.: 30 AF XY: 0.00226 AC XY: 1643 AN XY: 727048

African (AFR) AF: 0.000299 AC: 10 AN: 33454

American (AMR) AF: 0.00293 AC: 131 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00126 AC: 109 AN: 86234

European-Finnish (FIN) AF: 0.00320 AC: 171 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00252 AC: 2801 AN: 1111774

Other (OTH) AF: 0.00247 AC: 149 AN: 60384

GnomAD4 genome AF: 0.00194 AC: 296 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.00206 AC XY: 153 AN XY: 74432

African (AFR) AF: 0.000433 AC: 18 AN: 41566

American (AMR) AF: 0.00295 AC: 45 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00273 AC: 186 AN: 68018

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00204 Hom.: 1

Bravo AF: 0.00160

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00198 AC: 240

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.028
DANN	Benign	0.53
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.10
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.0070
Sift	Benign	0.57	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.048
MVP		0.12
MPC		0.040
ClinPred		0.0025	T
GERP RS		-3.6
Varity_R		0.023
gMVP		0.31
Mutation Taster		=98/2	polymorphism

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: rs140230044; hg19: chr8-24170956;