rs3807404

Positions:

• chr7-38513026-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.151-9322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,108 control chromosomes in the GnomAD database, including 4,833 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 0.24 (4833 hom., cov: 32)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPH	NM_001635.4	c.151-9322T>C		intron_variant		ENST00000356264.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPH	ENST00000356264.7	c.151-9322T>C		intron_variant		1	NM_001635.4	P3
AMPH	ENST00000325590.9	c.151-9322T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36757 AN: 151990 Hom.: 4834 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.242 AC: 36771 AN: 152108 Hom.: 4833 Cov.: 32 AF XY: 0.244 AC XY: 18165 AN XY: 74348

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.211

Alfa AF: 0.251 Hom.: 944

Bravo AF: 0.221

Asia WGS AF: 0.210 AC: 732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.4
DANN	Benign	0.77

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: rs3807404; hg19: chr7-38552626;