rs4215

Positions:

• chr7-99971771-G-A
• chr7-99971771-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001185.4(AZGP1):​c.312C>T​(p.Ile104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,613,272 control chromosomes in the GnomAD database, including 128,272 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 0.33 (10019 hom., cov: 31)
  • Exomes 𝑓: 0.40 (118253 hom.)
• Consequence: AZGP1 NM_001185.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

AZGP1 (HGNC:910): (alpha-2-glycoprotein 1, zinc-binding) Involved in cell adhesion and detection of chemical stimulus involved in sensory perception of bitter taste. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AZGP1	NM_001185.4	c.312C>T	p.Ile104=	synonymous_variant	2/4	ENST00000292401.9	NP_001176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AZGP1	ENST00000292401.9	c.312C>T	p.Ile104=	synonymous_variant	2/4	1	NM_001185.4	ENSP00000292401	P1
AZGP1	ENST00000411734.1	c.303C>T	p.Ile101=	synonymous_variant	2/3	1		ENSP00000396093
AZGP1	ENST00000419575.1	c.140+84C>T		intron_variant		3		ENSP00000389942
AZGP1	ENST00000495765.1	n.334C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50847 AN: 151758 Hom.: 10016 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.411 AC: 103168 AN: 251316 Hom.: 22862 AF XY: 0.413 AC XY: 56091 AN XY: 135826

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.497

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.665

Gnomad SAS exome AF: 0.424

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.397 AC: 579597 AN: 1461396 Hom.: 118253 Cov.: 49 AF XY: 0.399 AC XY: 290186 AN XY: 727028

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.637

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.335 AC: 50858 AN: 151876 Hom.: 10019 Cov.: 31 AF XY: 0.340 AC XY: 25253 AN XY: 74216

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.377

Alfa AF: 0.362 Hom.: 6579

Bravo AF: 0.338

Asia WGS AF: 0.474 AC: 1647 AN: 3478

EpiCase AF: 0.402

EpiControl AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.7
DANN	Benign	0.59

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: rs4215; hg19: chr7-99569394; COSMIC: COSV52797868; COSMIC: COSV52797868;