rs893412

Positions:

• chr7-38546623-C-A

Variant summary

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

The NM_001635.4(AMPH):​c.70-11612G>T 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 152,132 control chromosomes in the GnomAD database, including 1,386 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 (1386 hom., cov: 32)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPH	NM_001635.4	c.70-11612G>T		intron_variant		ENST00000356264.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPH	ENST00000356264.7	c.70-11612G>T		intron_variant		1	NM_001635.4	P3
AMPH	ENST00000325590.9	c.70-11612G>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16984 AN: 152016 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0845

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.112 AC: 16986 AN: 152132 Hom.: 1386 Cov.: 32 AF XY: 0.114 AC XY: 8486 AN XY: 74368

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0845

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.114

Alfa AF: 0.123 Hom.: 1753

Bravo AF: 0.115

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.69

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: rs893412; hg19: chr7-38586223;