rs893412

Variant names:

• chr7-38546623-C-A
• rs893412
• NM_001635.4:c.70-11612G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001635.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPH	NM_001635.4	MANE Select	c.70-11612G>T		intron	N/A	NP_001626.1
	AMPH	NM_139316.3		c.70-11612G>T		intron	N/A	NP_647477.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPH	ENST00000356264.7	TSL:1 MANE Select	c.70-11612G>T		intron	N/A	ENSP00000348602.2
	AMPH	ENST00000325590.9	TSL:1	c.70-11612G>T		intron	N/A	ENSP00000317441.5

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

African (AFR) AF: 0.0301 AC: 1249 AN: 41518

American (AMR) AF: 0.208 AC: 3177 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1723 AN: 5156

South Asian (SAS) AF: 0.204 AC: 984 AN: 4812

European-Finnish (FIN) AF: 0.0845 AC: 894 AN: 10584

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8359 AN: 67984

Other (OTH) AF: 0.114 AC: 240 AN: 2110

Alfa AF: 0.121 Hom.: 2198

Bravo AF: 0.115

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.69
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs893412; hg19: chr7-38586223;