rs1448905

Positions:

• chr2-206447191-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003812.4(ADAM23):​c.432+1667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,056 control chromosomes in the GnomAD database, including 10,805 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 0.37 (10805 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.432+1667T>C		intron_variant		ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.432+1667T>C		intron_variant			NP_001397914.1
ADAM23	XM_005246932.4	c.432+1667T>C		intron_variant			XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.432+1667T>C		intron_variant		1	NM_003812.4	ENSP00000264377	P4
ADAM23	ENST00000374415.7	c.432+1667T>C		intron_variant		5		ENSP00000363536	A1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57005 AN: 151938 Hom.: 10808 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.375 AC: 57017 AN: 152056 Hom.: 10805 Cov.: 32 AF XY: 0.369 AC XY: 27425 AN XY: 74310

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.387

Alfa AF: 0.404 Hom.: 19675

Bravo AF: 0.374

Asia WGS AF: 0.367 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1448905; hg19: chr2-207311915;