7-38417544-T-G

Variant names:

• chr7-38417544-T-G
• rs2270294
• NM_001635.4:c.1398+281A>C

Variant summary

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

The NM_001635.4(AMPH):​c.1398+281A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,250 control chromosomes in the GnomAD database, including 1,268 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 (1268 hom., cov: 33)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 3 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 = 0.233 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.1398+281A>C		intron	N/A	NP_001626.1
	AMPH	NM_139316.3		c.1272+4877A>C		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.1398+281A>C		intron	N/A	ENSP00000348602.2
	AMPH	ENST00000325590.9	TSL:1	c.1272+4877A>C		intron	N/A	ENSP00000317441.5
	AMPH	ENST00000441628.5	TSL:1	c.1044+4877A>C		intron	N/A	ENSP00000415085.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16543 AN: 152132 Hom.: 1266 Cov.: 33

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.109 AC: 16546 AN: 152250 Hom.: 1268 Cov.: 33 AF XY: 0.111 AC XY: 8286 AN XY: 74458

African (AFR) AF: 0.0267 AC: 1111 AN: 41570

American (AMR) AF: 0.214 AC: 3271 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1263 AN: 5176

South Asian (SAS) AF: 0.197 AC: 951 AN: 4824

European-Finnish (FIN) AF: 0.0891 AC: 945 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8435 AN: 67998

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.107 Hom.: 955

Bravo AF: 0.110

Asia WGS AF: 0.229 AC: 795 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	4.1
DANN	Benign	0.67
PhyloP100		-0.28
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: rs2270294; hg19: chr7-38457144;