rs4085933

Variant names:

• chr2-206606160-T-C
• rs4085933
• NM_003812.4:c.2360-3750T>C

Variant summary

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

The NM_003812.4(ADAM23):​c.2360-3750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,162 control chromosomes in the GnomAD database, including 13,102 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13102 hom., cov: 33)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 7 publications found

Genes affected

ADAM23 (HGNC:202): (ADAM metallopeptidase domain 23) 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. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.2360-3750T>C		intron_variant	Intron 24 of 25	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.2450+280T>C		intron_variant	Intron 25 of 25		NP_001397914.1
ADAM23	XM_005246932.4	c.2359+9998T>C		intron_variant	Intron 24 of 24		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.2360-3750T>C		intron_variant	Intron 24 of 25	1	NM_003812.4	ENSP00000264377.3
ADAM23	ENST00000374415.7	c.2450+280T>C		intron_variant	Intron 25 of 25	5		ENSP00000363536.3
ADAM23	ENST00000444281.1	c.181+9998T>C		intron_variant	Intron 2 of 2	3		ENSP00000406827.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61869 AN: 152044 Hom.: 13099 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.407 AC: 61873 AN: 152162 Hom.: 13102 Cov.: 33 AF XY: 0.404 AC XY: 30045 AN XY: 74396

African (AFR) AF: 0.281 AC: 11673 AN: 41514

American (AMR) AF: 0.371 AC: 5678 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1490 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2406 AN: 5176

South Asian (SAS) AF: 0.426 AC: 2050 AN: 4814

European-Finnish (FIN) AF: 0.464 AC: 4915 AN: 10582

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32246 AN: 68002

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.455 Hom.: 61051

Bravo AF: 0.396

Asia WGS AF: 0.486 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.61
PhyloP100		-2.3
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: rs4085933; hg19: chr2-207470884;