rs10487744

Variant names:

• chr7-38450573-C-T
• rs10487744
• NM_001635.4:c.1017+10710G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001635.4(AMPH):​c.1017+10710G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,148 control chromosomes in the GnomAD database, including 371 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 0.050 (371 hom., cov: 32)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPH	NM_001635.4	c.1017+10710G>A		intron_variant	Intron 11 of 20	ENST00000356264.7	NP_001626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPH	ENST00000356264.7	c.1017+10710G>A		intron_variant	Intron 11 of 20	1	NM_001635.4	ENSP00000348602.2
AMPH	ENST00000325590.9	c.1017+10710G>A		intron_variant	Intron 11 of 19	1		ENSP00000317441.5
AMPH	ENST00000441628.5	c.267+10710G>A		intron_variant	Intron 2 of 11	1		ENSP00000415085.1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7622 AN: 152028 Hom.: 369 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0502 AC: 7631 AN: 152148 Hom.: 371 Cov.: 32 AF XY: 0.0498 AC XY: 3707 AN XY: 74390

African (AFR) AF: 0.126 AC: 5212 AN: 41476

American (AMR) AF: 0.0245 AC: 375 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0770 AC: 372 AN: 4830

European-Finnish (FIN) AF: 0.0378 AC: 400 AN: 10590

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1079 AN: 68002

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

Alfa AF: 0.0348 Hom.: 39

Bravo AF: 0.0518

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.44
PhyloP100		-0.028
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: rs10487744; hg19: chr7-38490173;