rs6828523

Positions:

• chr4-174925275-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014269.4(ADAM29):​c.-451+4483C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,004 control chromosomes in the GnomAD database, including 4,043 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 0.20 (4043 hom., cov: 32)
• Consequence: ADAM29 NM_014269.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM29	NM_014269.4	c.-451+4483C>A		intron_variant		ENST00000359240.7	NP_055084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM29	ENST00000359240.7	c.-451+4483C>A		intron_variant		2	NM_014269.4	ENSP00000352177	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30495 AN: 151884 Hom.: 4032 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.201 AC: 30545 AN: 152004 Hom.: 4043 Cov.: 32 AF XY: 0.200 AC XY: 14835 AN XY: 74280

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0632

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.175

Alfa AF: 0.151 Hom.: 738

Bravo AF: 0.216

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.66

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: rs6828523; hg19: chr4-175846426;