rs201997

chr8-39726649-C-Gchr8-39726649-C-T

Variant summary

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

The NM_014237.3(ADAM18):c.2177+2742C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,034 control chromosomes in the GnomAD database, including 6,779 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 0.27 (6779 hom., cov: 31)
• Consequence: ADAM18 NM_014237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

Genes affected

ADAM18 (HGNC:196): (ADAM metallopeptidase domain 18) 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 biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature sperm surface protein. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM18	NM_014237.3	c.2177+2742C>G		intron_variant		ENST00000265707.10
ADAM18	NM_001320313.2	c.2105+2742C>G		intron_variant
ADAM18	NR_135201.2	n.1870+2742C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM18	ENST00000265707.10	c.2177+2742C>G		intron_variant		1	NM_014237.3	P1
ADAM18	ENST00000379866.5	c.2105+2742C>G		intron_variant		1
ADAM18	ENST00000520087.5	c.*1467+2742C>G		intron_variant, NMD_transcript_variant		1
ADAM18	ENST00000523755.5	n.639+2742C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41021 AN: 151916 Hom.: 6771 Cov.: 31

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.270 AC: 41026 AN: 152034 Hom.: 6779 Cov.: 31 AF XY: 0.269 AC XY: 19993 AN XY: 74278

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.279

Alfa AF: 0.221 Hom.: 627

Bravo AF: 0.263

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.0
Dann	Benign	0.38

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: rs201997; hg19: chr8-39584168;