7-38560576-A-G

Position:

• chr7-38560576-A-G

Variant summary

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

The NM_001635.4(AMPH):​c.70-25565T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,240 control chromosomes in the GnomAD database, including 54,570 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 0.85 (54570 hom., cov: 34)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPH	NM_001635.4	c.70-25565T>C		intron_variant		ENST00000356264.7	NP_001626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPH	ENST00000356264.7	c.70-25565T>C		intron_variant		1	NM_001635.4	ENSP00000348602.2
AMPH	ENST00000325590.9	c.70-25565T>C		intron_variant		1		ENSP00000317441.5

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128615 AN: 152122 Hom.: 54519 Cov.: 34

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.846 AC: 128725 AN: 152240 Hom.: 54570 Cov.: 34 AF XY: 0.847 AC XY: 63065 AN XY: 74440

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.829

Alfa AF: 0.848 Hom.: 55834

Bravo AF: 0.839

Asia WGS AF: 0.865 AC: 3008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.9
DANN	Benign	0.43

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: rs6967370; hg19: chr7-38600176;