8-39639492-C-T

Variant names:

• chr8-39639492-C-T
• rs3852339
• NM_014237.3:c.909+946C>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.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
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM18	NM_014237.3	MANE Select	c.909+946C>T		intron	N/A	NP_055052.1	Q9Y3Q7-1
	ADAM18	NM_001320313.2		c.837+946C>T		intron	N/A	NP_001307242.1	Q9Y3Q7-2
	ADAM18	NR_135201.2		n.786+946C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM18	ENST00000265707.10	TSL:1 MANE Select	c.909+946C>T		intron	N/A	ENSP00000265707.5	Q9Y3Q7-1
	ADAM18	ENST00000379866.5	TSL:1	c.837+946C>T		intron	N/A	ENSP00000369195.1	Q9Y3Q7-2
	ADAM18	ENST00000520087.5	TSL:1	n.*383+946C>T		intron	N/A	ENSP00000428083.1	E5RK96

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

African (AFR) AF: 0.384 AC: 15895 AN: 41394

American (AMR) AF: 0.565 AC: 8605 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3466

East Asian (EAS) AF: 0.255 AC: 1314 AN: 5154

South Asian (SAS) AF: 0.639 AC: 3081 AN: 4824

European-Finnish (FIN) AF: 0.579 AC: 6116 AN: 10556

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.650 AC: 44108 AN: 67844

Other (OTH) AF: 0.558 AC: 1178 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.64
PhyloP100		-0.55
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: rs3852339; hg19: chr8-39497011;