chr4-174894978-T-C

Variant names:

• chr4-174894978-T-C
• rs6858430
• ENST00000507969.5:n.345-36008T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000507969.5(ADAM29):​n.345-36008T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,124 control chromosomes in the GnomAD database, including 42,291 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 0.74 (42291 hom., cov: 34)
• Consequence: ADAM29 ENST00000507969.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 5 publications found

Genes affected

ADAM29 (HGNC:207): (ADAM metallopeptidase domain 29) 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 biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is highly expressed in testis and may be involved in human spermatogenesis. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM29	ENST00000507969.5	n.345-36008T>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112675 AN: 152006 Hom.: 42246 Cov.: 34

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.741 AC: 112777 AN: 152124 Hom.: 42291 Cov.: 34 AF XY: 0.736 AC XY: 54695 AN XY: 74354

African (AFR) AF: 0.725 AC: 30085 AN: 41518

American (AMR) AF: 0.639 AC: 9765 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2591 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2520 AN: 5180

South Asian (SAS) AF: 0.759 AC: 3659 AN: 4818

European-Finnish (FIN) AF: 0.732 AC: 7754 AN: 10586

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.793 AC: 53918 AN: 67964

Other (OTH) AF: 0.725 AC: 1528 AN: 2108

Alfa AF: 0.775 Hom.: 158880

Bravo AF: 0.731

Asia WGS AF: 0.632 AC: 2191 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6858430; hg19: chr4-175816129;