rs3778884

Positions:

• chr7-38439620-G-A
• chr7-38439620-G-C

Variant summary

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

The NM_001635.4(AMPH):​c.1018-3232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,982 control chromosomes in the GnomAD database, including 8,405 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 (8405 hom., cov: 32)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPH	NM_001635.4	c.1018-3232C>T		intron_variant		ENST00000356264.7	NP_001626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPH	ENST00000356264.7	c.1018-3232C>T		intron_variant		1	NM_001635.4	ENSP00000348602.2
AMPH	ENST00000325590.9	c.1018-3232C>T		intron_variant		1		ENSP00000317441.5
AMPH	ENST00000441628.5	c.268-3232C>T		intron_variant		1		ENSP00000415085.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50200 AN: 151864 Hom.: 8399 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.331 AC: 50239 AN: 151982 Hom.: 8405 Cov.: 32 AF XY: 0.326 AC XY: 24237 AN XY: 74290

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.344

Alfa AF: 0.343 Hom.: 8970

Bravo AF: 0.340

Asia WGS AF: 0.341 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.29

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: rs3778884; hg19: chr7-38479220;