rs7832578

Variant names:

• chr8-39019896-C-T
• rs7832578
• NM_003816.3:c.672+978C>T

Variant summary

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

The NM_003816.3(ADAM9):​c.672+978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,060 control chromosomes in the GnomAD database, including 11,207 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 0.37 (11207 hom., cov: 33)
• Consequence: ADAM9 NM_003816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 publications found

Genes affected

ADAM9 (HGNC:216): (ADAM metallopeptidase domain 9) 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 interacts with SH3 domain-containing proteins, binds mitotic arrest deficient 2 beta protein, and is also involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. Several alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2010]

ADAM9 Gene-Disease associations (from GenCC):

• ADAM9-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM9	NM_003816.3	c.672+978C>T		intron_variant	Intron 7 of 21	ENST00000487273.7	NP_003807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM9	ENST00000487273.7	c.672+978C>T		intron_variant	Intron 7 of 21	1	NM_003816.3	ENSP00000419446.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56936 AN: 151942 Hom.: 11207 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.375 AC: 56972 AN: 152060 Hom.: 11207 Cov.: 33 AF XY: 0.370 AC XY: 27499 AN XY: 74326

African (AFR) AF: 0.510 AC: 21143 AN: 41488

American (AMR) AF: 0.326 AC: 4976 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5168

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3252 AN: 10562

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22633 AN: 67954

Other (OTH) AF: 0.354 AC: 750 AN: 2116

Alfa AF: 0.342 Hom.: 5310

Bravo AF: 0.378

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.47
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7832578; hg19: chr8-38877415;