8-39639492-C-T

Position:

• chr8-39639492-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.909+946C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,766 control chromosomes in the GnomAD database, including 24,204 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 0.55 (24204 hom., cov: 31)
• Consequence: ADAM18 NM_014237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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]

ADAM18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM18	NM_014237.3	c.909+946C>T		intron_variant		ENST00000265707.10	NP_055052.1
ADAM18	NM_001320313.2	c.837+946C>T		intron_variant			NP_001307242.1
ADAM18	NR_135201.2	n.786+946C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM18	ENST00000265707.10	c.909+946C>T		intron_variant		1	NM_014237.3	ENSP00000265707.5
ADAM18	ENST00000379866.5	c.837+946C>T		intron_variant		1		ENSP00000369195.1
ADAM18	ENST00000520087.5	n.*383+946C>T		intron_variant		1		ENSP00000428083.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83318 AN: 151644 Hom.: 24205 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.628

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.549 AC: 83340 AN: 151766 Hom.: 24204 Cov.: 31 AF XY: 0.546 AC XY: 40480 AN XY: 74164

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.558

Alfa AF: 0.592 Hom.: 3428

Bravo AF: 0.537

Asia WGS AF: 0.456 AC: 1582 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.64

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: rs3852339; hg19: chr8-39497011;