Genetic Variant NM_001110.4:c.207-8912C>G (chr15-58691226-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001110.4(ADAM10):c.207-8912C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 856,660 control chromosomes in the GnomAD database, including 87,983 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 0.49 ( 20887 hom., cov: 31)

Exomes 𝑓: 0.41 ( 67096 hom. )

Consequence

ADAM10
NM_001110.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.332

Variant links:

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]

ADAM10 links:

HSP90AB4P (HGNC:32538): (heat shock protein 90 alpha family class B member 4, pseudogene) Predicted to enable ATP binding activity; disordered domain specific binding activity; and unfolded protein binding activity. Predicted to be involved in cellular response to heat; protein folding; and protein stabilization. Predicted to be part of protein-containing complex. Predicted to be active in cytosol; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSP90AB4P links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADAM10	NM_001110.4 link	c.207-8912C>G	intron_variant	Intron 2 of 15	ENST00000260408.8	NP_001101.1	O14672-1A0A024R5U5
ADAM10	NM_001320570.2 link	c.207-8912C>G	intron_variant	Intron 2 of 14		NP_001307499.1
HSP90AB4P	NR_073415.2 link	n.2382C>G	non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408.8 link	c.207-8912C>G		intron_variant	Intron 2 of 15	1	NM_001110.4	ENSP00000260408.3		O14672-1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73893

AN:

151794

Hom.:

20838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.743

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.528

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.444

GnomAD3 exomes

AF:

0.461

AC:

106366

AN:

230592

Hom.:

27653

AF XY:

0.448

AC XY:

55820

AN XY:

124502

show subpopulations

Gnomad AFR exome

AF:

0.758

Gnomad AMR exome

AF:

0.557

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.843

Gnomad SAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.476

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

AF:

0.410

AC:

288823

AN:

704748

Hom.:

67096

Cov.:

AF XY:

0.409

AC XY:

154074

AN XY:

376728

show subpopulations

Gnomad4 AFR exome

AF:

0.751

Gnomad4 AMR exome

AF:

0.551

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.871

Gnomad4 SAS exome

AF:

0.511

Gnomad4 FIN exome

AF:

0.471

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.487

AC:

74004

AN:

151912

Hom.:

20887

Cov.:

AF XY:

0.496

AC XY:

36829

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.744

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.841

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.274

Hom.:

1017

Bravo

AF:

0.502

Asia WGS

AF:

0.691

AC:

2398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.58

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over