Genetic Variant GOSR2:c.-23C>A (chr17-46923170-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_004287.5(GOSR2):c.-23C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,484,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

GOSR2
NM_004287.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.361

Publications

0 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:

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

GOSR2-DT links:

Genome browser will be placed here

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=-0.78).

BP6

Variant 17-46923170-C-A is Benign according to our data. Variant chr17-46923170-C-A is described in ClinVar as Benign. ClinVar VariationId is 205626.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000427 (65/152330) while in subpopulation NFE AF = 0.000779 (53/68016). AF 95% confidence interval is 0.000612. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. 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.-23C>A	5_prime_UTR	Exon 1 of 6	NP_004278.2
GOSR2	NM_001321133.2		c.-23C>A	5_prime_UTR	Exon 1 of 7	NP_001308062.1	I3NI02
GOSR2	NM_054022.4		c.-23C>A	5_prime_UTR	Exon 1 of 7	NP_473363.1	O14653-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.-23C>A	5_prime_UTR	Exon 1 of 6	ENSP00000492751.1	O14653-1
GOSR2	ENST00000225567.9	TSL:1	c.-23C>A	5_prime_UTR	Exon 1 of 7	ENSP00000225567.4	O14653-2
GOSR2	ENST00000640621.1	TSL:1	c.-23C>A	5_prime_UTR	Exon 1 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000443

AC:

AN:

153328

AF XY:

0.000394

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000667

Gnomad NFE exome

AF:

0.000767

Gnomad OTH exome

AF:

0.00321

GnomAD4 exome

AF:

0.000677

AC:

902

AN:

1332640

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

439

AN XY:

660612

show subpopulations

African (AFR)

AF:

0.0000984

AC:

AN:

30502

American (AMR)

AF:

0.000505

AC:

AN:

35630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24720

East Asian (EAS)

AF:

0.00

AC:

AN:

35420

South Asian (SAS)

AF:

0.00

AC:

AN:

77928

European-Finnish (FIN)

AF:

0.0000614

AC:

AN:

48834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

0.000830

AC:

845

AN:

1018418

Other (OTH)

AF:

0.000593

AC:

AN:

55682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000427

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41578

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.000434

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.36

PromoterAI

0.060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=297/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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