rs6828523

Variant names:

• chr4-174925275-C-A
• rs6828523
• NM_014269.4:c.-451+4483C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 69 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014269.4. 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
	ADAM29	NM_014269.4	MANE Select	c.-451+4483C>A		intron	N/A	NP_055084.3	A0A140VJD8
	ADAM29	NM_001130703.1		c.-370+4483C>A		intron	N/A	NP_001124175.1	A0A140VJD8
	ADAM29	NM_001130704.1		c.-450-5711C>A		intron	N/A	NP_001124176.1	A0A140VJD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM29	ENST00000359240.7	TSL:2 MANE Select	c.-451+4483C>A		intron	N/A	ENSP00000352177.3	Q9UKF5-1
	ADAM29	ENST00000404450.8	TSL:1	c.-450-5711C>A		intron	N/A	ENSP00000384229.3	Q9UKF5-1
	ADAM29	ENST00000445694.5	TSL:1	c.-370+4483C>A		intron	N/A	ENSP00000414544.1	Q9UKF5-1

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

African (AFR) AF: 0.375 AC: 15544 AN: 41442

American (AMR) AF: 0.172 AC: 2631 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3464

East Asian (EAS) AF: 0.251 AC: 1295 AN: 5156

South Asian (SAS) AF: 0.191 AC: 920 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1310 AN: 10546

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8146 AN: 67980

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.154 Hom.: 4699

Bravo AF: 0.216

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.66
PhyloP100		-1.2
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: rs6828523; hg19: chr4-175846426;