Genetic Variant ENST00000640621.1:c.*625T>C (chr17-46935905-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000640621.1(GOSR2):c.*625T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 985,566 control chromosomes in the GnomAD database, including 9,410 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 0.091 ( 907 hom., cov: 32)

Exomes 𝑓: 0.14 ( 8503 hom. )

Consequence

GOSR2
ENST00000640621.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

126 publications found

Variant links:

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

GOSR2 links:

ENSG00000262633 (HGNC:):

ENSG00000262633 links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

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new If you want to explore the variant's impact on the transcript ENST00000640621.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000640621.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GOSR2	NM_004287.5	MANE Select	c.477+736T>C	intron	N/A	NP_004278.2
GOSR2	NM_001012511.3		c.*625T>C	3_prime_UTR	Exon 5 of 5	NP_001012529.1	O14653-3
GOSR2	NM_001321133.2		c.477+736T>C	intron	N/A	NP_001308062.1	I3NI02

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GOSR2	ENST00000640621.1	TSL:1	c.*625T>C	3_prime_UTR	Exon 5 of 5	ENSP00000492830.1	O14653-3
GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.477+736T>C	intron	N/A	ENSP00000492751.1	O14653-1
GOSR2	ENST00000225567.9	TSL:1	c.477+736T>C	intron	N/A	ENSP00000225567.4	O14653-2

Frequencies

GnomAD3 genomes

AF:

0.0912

AC:

13883

AN:

152154

Hom.:

909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.0754

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0391

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.0952

GnomAD4 exome

AF:

0.139

AC:

115622

AN:

833294

Hom.:

8503

Cov.:

AF XY:

0.139

AC XY:

53510

AN XY:

384876

show subpopulations

African (AFR)

AF:

0.0132

AC:

208

AN:

15788

American (AMR)

AF:

0.0709

AC:

AN:

988

Ashkenazi Jewish (ASJ)

AF:

0.0528

AC:

272

AN:

5152

East Asian (EAS)

AF:

0.00138

AC:

AN:

3632

South Asian (SAS)

AF:

0.0394

AC:

648

AN:

16450

European-Finnish (FIN)

AF:

0.195

AC:

137

AN:

702

Middle Eastern (MID)

AF:

0.0637

AC:

103

AN:

1618

European-Non Finnish (NFE)

AF:

0.146

AC:

111031

AN:

761666

Other (OTH)

AF:

0.115

AC:

3148

AN:

27298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4613

9226

13840

18453

23066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5316

10632

15948

21264

26580

<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:

0.0911

AC:

13876

AN:

152272

Hom.:

907

Cov.:

AF XY:

0.0903

AC XY:

6725

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0227

AC:

945

AN:

41562

American (AMR)

AF:

0.0753

AC:

1153

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0507

AC:

176

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4826

European-Finnish (FIN)

AF:

0.181

AC:

1922

AN:

10606

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9109

AN:

68004

Other (OTH)

AF:

0.0942

AC:

199

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

627

1253

1880

2506

3133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.116

Hom.:

3858

Bravo

AF:

0.0819

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over