dbSNP rs3803947: SNPH:c.*2268G>A (chr20-1308322-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001318234.2(SNPH):c.*2268G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,442 control chromosomes in the GnomAD database, including 17,360 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 0.47 ( 17337 hom., cov: 33)

Exomes 𝑓: 0.37 ( 23 hom. )

Consequence

SNPH
NM_001318234.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.162

Publications

7 publications found

Variant links:

Genes affected

SNPH (HGNC:15931): (syntaphilin) Syntaxin-1, synaptobrevin/VAMP, and SNAP25 interact to form the SNARE complex, which is required for synaptic vesicle docking and fusion. The protein encoded by this gene is membrane-associated and inhibits SNARE complex formation by binding free syntaxin-1. Expression of this gene appears to be brain-specific. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SNPH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNPH	NM_001318234.2 link	c.*2268G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000381867.6	NP_001305163.1	O15079-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SNPH	ENST00000381867.6 link	c.*2268G>A	3_prime_UTR_variant	Exon 7 of 7	1	NM_001318234.2	ENSP00000371291.1	O15079-2
SNPH	ENST00000614659.1 link	c.*2268G>A	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000479696.1	O15079-2
SNPH	ENST00000381873.7 link	c.*2268G>A	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000371297.3	O15079-1

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70865

AN:

152012

Hom.:

17316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.0901

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.372

AC:

116

AN:

312

Hom.:

Cov.:

AF XY:

0.376

AC XY:

AN XY:

234

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.125

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.384

AC:

AN:

258

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.466

AC:

70924

AN:

152130

Hom.:

17337

Cov.:

AF XY:

0.455

AC XY:

33841

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.580

AC:

24079

AN:

41522

American (AMR)

AF:

0.429

AC:

6550

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1626

AN:

3466

East Asian (EAS)

AF:

0.0895

AC:

463

AN:

5172

South Asian (SAS)

AF:

0.303

AC:

1459

AN:

4822

European-Finnish (FIN)

AF:

0.373

AC:

3954

AN:

10588

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31324

AN:

67968

Other (OTH)

AF:

0.455

AC:

960

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1876

3752

5628

7504

9380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.463

Hom.:

2085

Bravo

AF:

0.474

Asia WGS

AF:

0.231

AC:

803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

(source)

DANN

Benign

0.87

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over