dbSNP rs8208: SRP14:p.Leu94Leu (chr15-40036464-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_003134.6(SRP14):c.280C>T(p.Leu94Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.668 in 1,613,542 control chromosomes in the GnomAD database, including 370,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27466 hom., cov: 32)

Exomes 𝑓: 0.68 ( 343053 hom. )

Consequence

SRP14
NM_003134.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.69

Publications

25 publications found

Variant links:

Genes affected

SRP14 (HGNC:11299): (signal recognition particle 14) Enables RNA binding activity. Involved in protein targeting to ER. Located in nucleus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

SRP14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 15-40036464-G-A is Benign according to our data. Variant chr15-40036464-G-A is described in ClinVar as Benign. ClinVar VariationId is 402823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP14	NM_003134.6 link	c.280C>T	p.Leu94Leu	synonymous_variant	Exon 5 of 5	ENST00000267884.11	NP_003125.3	P37108
SRP14	NM_001309434.1 link	c.136C>T	p.Leu46Leu	synonymous_variant	Exon 6 of 6		NP_001296363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP14	ENST00000267884.11 link	c.280C>T	p.Leu94Leu	synonymous_variant	Exon 5 of 5	1	NM_003134.6	ENSP00000267884.6		P37108

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87754

AN:

151794

Hom.:

27465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.673

Gnomad MID

AF:

0.666

Gnomad NFE

AF:

0.718

Gnomad OTH

AF:

0.604

GnomAD2 exomes

AF:

0.606

AC:

151508

AN:

250066

AF XY:

0.620

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.701

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.685

Gnomad NFE exome

AF:

0.715

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.677

AC:

989993

AN:

1461630

Hom.:

343053

Cov.:

AF XY:

0.678

AC XY:

492973

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.351

AC:

11720

AN:

33426

American (AMR)

AF:

0.459

AC:

20521

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

18408

AN:

26134

East Asian (EAS)

AF:

0.276

AC:

10950

AN:

39694

South Asian (SAS)

AF:

0.626

AC:

53980

AN:

86234

European-Finnish (FIN)

AF:

0.683

AC:

36477

AN:

53402

Middle Eastern (MID)

AF:

0.668

AC:

3855

AN:

5768

European-Non Finnish (NFE)

AF:

0.715

AC:

795018

AN:

1111870

Other (OTH)

AF:

0.647

AC:

39064

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

17941

35883

53824

71766

89707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19540

39080

58620

78160

97700

<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:

0.578

AC:

87765

AN:

151912

Hom.:

27466

Cov.:

AF XY:

0.574

AC XY:

42612

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.358

AC:

14810

AN:

41364

American (AMR)

AF:

0.524

AC:

7990

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2441

AN:

3470

East Asian (EAS)

AF:

0.268

AC:

1384

AN:

5168

South Asian (SAS)

AF:

0.623

AC:

3002

AN:

4820

European-Finnish (FIN)

AF:

0.673

AC:

7084

AN:

10530

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.718

AC:

48846

AN:

67996

Other (OTH)

AF:

0.603

AC:

1271

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1725

3450

5176

6901

8626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.650

Hom.:

20250

Bravo

AF:

0.552

Asia WGS

AF:

0.413

AC:

1440

AN:

3478

EpiCase

AF:

0.716

EpiControl

AF:

0.707

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=79/21

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over