chr7-38461273-A-G

Variant names:

• chr7-38461273-A-G
• rs201791183
• NM_001635.4:c.1017+10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001635.4(AMPH):​c.1017+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,613,586 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (104 hom.)
• Consequence: AMPH NM_001635.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.132

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 7-38461273-A-G is Benign according to our data. Variant chr7-38461273-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 786899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPH	NM_001635.4	c.1017+10T>C		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+10T>C		intron_variant	Intron 11 of 20	1	NM_001635.4	ENSP00000348602.2
AMPH	ENST00000325590.9	c.1017+10T>C		intron_variant	Intron 11 of 19	1		ENSP00000317441.5
AMPH	ENST00000441628.5	c.267+10T>C		intron_variant	Intron 2 of 11	1		ENSP00000415085.1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3111 AN: 152182 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00496 AC: 1248 AN: 251394 AF XY: 0.00372

Gnomad AFR exome AF: 0.0695

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00207 AC: 3026 AN: 1461286 Hom.: 104 Cov.: 31 AF XY: 0.00178 AC XY: 1295 AN XY: 726956

African (AFR) AF: 0.0749 AC: 2506 AN: 33454

American (AMR) AF: 0.00284 AC: 127 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00379 AC: 21 AN: 5534

European-Non Finnish (NFE) AF: 0.0000908 AC: 101 AN: 1111790

Other (OTH) AF: 0.00416 AC: 251 AN: 60340

GnomAD4 genome AF: 0.0205 AC: 3125 AN: 152300 Hom.: 103 Cov.: 32 AF XY: 0.0201 AC XY: 1496 AN XY: 74474

African (AFR) AF: 0.0715 AC: 2970 AN: 41554

American (AMR) AF: 0.00693 AC: 106 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68020

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.00955 Hom.: 14

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.6
DANN	Benign	0.78
PhyloP100		0.13
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

Publications

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Other links and lift over

dbSNP: rs201791183; hg19: chr7-38500873;