8-39690859-C-T

Variant names:

• chr8-39690859-C-T
• rs1349547
• NM_014237.3:c.1822-1741C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAM18	NM_014237.3	c.1822-1741C>T		intron_variant	Intron 16 of 19	ENST00000265707.10	NP_055052.1
ADAM18	NM_001320313.2	c.1750-1741C>T		intron_variant	Intron 15 of 18		NP_001307242.1
ADAM18	NR_135201.2	n.1515-1741C>T		intron_variant	Intron 14 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM18	ENST00000265707.10	c.1822-1741C>T		intron_variant	Intron 16 of 19	1	NM_014237.3	ENSP00000265707.5

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

African (AFR) AF: 0.587 AC: 24325 AN: 41428

American (AMR) AF: 0.349 AC: 5336 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3876 AN: 5156

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4814

European-Finnish (FIN) AF: 0.322 AC: 3399 AN: 10554

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16983 AN: 67952

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.290 Hom.: 15337

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
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1349547; hg19: chr8-39548378;