rs4775085

Positions:

• chr15-58657792-G-A
• chr15-58657792-G-C
• chr15-58657792-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001110.4(ADAM10):​c.585+7305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 151,972 control chromosomes in the GnomAD database, including 95 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 0.030 (95 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

Genes affected

ADAM10 (HGNC:188): (ADAM metallopeptidase domain 10) Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.03 (4555/151972) while in subpopulation NFE AF= 0.0483 (3281/67982). AF 95% confidence interval is 0.0469. There are 95 homozygotes in gnomad4. There are 2129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4555 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM10	NM_001110.4	c.585+7305C>T		intron_variant		ENST00000260408.8	NP_001101.1
ADAM10	NM_001320570.2	c.585+7305C>T		intron_variant			NP_001307499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408.8	c.585+7305C>T		intron_variant		1	NM_001110.4	ENSP00000260408	P1

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4558 AN: 151862 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.00888

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0297

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

GnomAD4 genome AF: 0.0300 AC: 4555 AN: 151972 Hom.: 95 Cov.: 32 AF XY: 0.0287 AC XY: 2129 AN XY: 74270

Gnomad4 AFR AF: 0.00885

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0483

Gnomad4 OTH AF: 0.0290

Alfa AF: 0.0381 Hom.: 149

Bravo AF: 0.0281

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs4775085; hg19: chr15-58949991;