chr8-39690859-C-T

Position:

• chr8-39690859-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.1822-1741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,950 control chromosomes in the GnomAD database, including 12,929 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 0.38 (12929 hom., cov: 32)
• Consequence: ADAM18 NM_014237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM18	NM_014237.3	c.1822-1741C>T		intron_variant		ENST00000265707.10	NP_055052.1
ADAM18	NM_001320313.2	c.1750-1741C>T		intron_variant			NP_001307242.1
ADAM18	NR_135201.2	n.1515-1741C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM18	ENST00000265707.10	c.1822-1741C>T		intron_variant		1	NM_014237.3	ENSP00000265707	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57401 AN: 151830 Hom.: 12900 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.378 AC: 57489 AN: 151950 Hom.: 12929 Cov.: 32 AF XY: 0.383 AC XY: 28419 AN XY: 74254

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.361

Alfa AF: 0.263 Hom.: 7631

Bravo AF: 0.393

Asia WGS AF: 0.537 AC: 1869 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	1.1
DANN	Benign	0.33

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: rs1349547; hg19: chr8-39548378;