NM_001110.4:c.*7777A>G

Variant names:

• chr15-58589770-T-C
• rs1869135
• NM_001110.4:c.*7777A>G

Variant summary

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

The NM_001110.4(ADAM10):​c.*7777A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,100 control chromosomes in the GnomAD database, including 4,585 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 0.24 (4582 hom., cov: 32)
  • Exomes 𝑓: 0.45 (3 hom.)
• Consequence: ADAM10 NM_001110.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

ENSG00000259250 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM10	NM_001110.4	c.*7777A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000260408.8	NP_001101.1
ADAM10	NM_001320570.2	c.*7777A>G		3_prime_UTR_variant	Exon 15 of 15		NP_001307499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408	c.*7777A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_001110.4	ENSP00000260408.3
ENSG00000259250	ENST00000560594.1	n.407-1771T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36038 AN: 151960 Hom.: 4582 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.438 AC XY: 7 AN XY: 16

Gnomad4 AFR exome AF: 0.750

Gnomad4 NFE exome AF: 0.389

GnomAD4 genome AF: 0.237 AC: 36054 AN: 152078 Hom.: 4582 Cov.: 32 AF XY: 0.239 AC XY: 17788 AN XY: 74318

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.257

Alfa AF: 0.227 Hom.: 8443

Bravo AF: 0.248

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.31

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: rs1869135; hg19: chr15-58881969;