7-2723468-C-T

Variant names:

• chr7-2723468-C-T
• rs798544
• ENST00000489665.1:n.550+13652C>T

Variant summary

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

The NM_001384740.1(AMZ1):​c.948+13652C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,188 control chromosomes in the GnomAD database, including 5,251 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 0.25 (5251 hom., cov: 33)
• Consequence: AMZ1 NM_001384740.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 70 publications found

Genes affected

AMZ1 (HGNC:22231): (archaelysin family metallopeptidase 1) Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

GNA12 (HGNC:4380): (G protein subunit alpha 12) Predicted to enable D5 dopamine receptor binding activity; G-protein beta/gamma-subunit complex binding activity; and GTPase activity. Involved in regulation of TOR signaling and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384740.1. 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
	AMZ1	NM_001384740.1		c.948+13652C>T		intron	N/A	NP_001371669.1
	AMZ1	NM_001321766.2		c.948+13652C>T		intron	N/A	NP_001308695.1
	AMZ1	NM_001384742.1		c.779-1013C>T		intron	N/A	NP_001371671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMZ1	ENST00000489665.1	TSL:1	n.550+13652C>T		intron	N/A
	GNA12	ENST00000715274.1		n.*1926-1330G>A		intron	N/A	ENSP00000520443.1	Q03113-1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38045 AN: 152070 Hom.: 5249 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.250 AC: 38058 AN: 152188 Hom.: 5251 Cov.: 33 AF XY: 0.253 AC XY: 18787 AN XY: 74398

African (AFR) AF: 0.149 AC: 6181 AN: 41554

American (AMR) AF: 0.284 AC: 4338 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 855 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1126 AN: 5184

South Asian (SAS) AF: 0.154 AC: 742 AN: 4818

European-Finnish (FIN) AF: 0.384 AC: 4065 AN: 10584

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19863 AN: 67964

Other (OTH) AF: 0.254 AC: 536 AN: 2114

Alfa AF: 0.277 Hom.: 28935

Bravo AF: 0.240

Asia WGS AF: 0.236 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs798544; hg19: chr7-2763102; COSMIC: COSV51738339;