rs2072506

Positions:

• chr7-38462795-A-T

Variant summary

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

The NM_001635.4(AMPH):​c.888+180T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,204 control chromosomes in the GnomAD database, including 1,394 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 0.11 (1394 hom., cov: 32)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

Genes affected

AMPH (HGNC:471): (amphiphysin) This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff-man syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPH	NM_001635.4	c.888+180T>A		intron_variant		ENST00000356264.7	NP_001626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPH	ENST00000356264.7	c.888+180T>A		intron_variant		1	NM_001635.4	ENSP00000348602	P3
AMPH	ENST00000325590.9	c.888+180T>A		intron_variant		1		ENSP00000317441	A2
AMPH	ENST00000441628.5	c.139+180T>A		intron_variant		1		ENSP00000415085

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17091 AN: 152086 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.112 AC: 17098 AN: 152204 Hom.: 1394 Cov.: 32 AF XY: 0.115 AC XY: 8539 AN XY: 74422

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.124

Alfa AF: 0.116 Hom.: 160

Bravo AF: 0.117

Asia WGS AF: 0.241 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.80

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: rs2072506; hg19: chr7-38502395; COSMIC: COSV57743362;