dbSNP rs187709513: GET4:p.Val215Val (chr7-892317-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_015949.3(GET4):c.645C>T(p.Val215Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,594,456 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00096 ( 22 hom. )

Consequence

GET4
NM_015949.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.483

Publications

0 publications found

Variant links:

Genes affected

GET4 (HGNC:21690): (guided entry of tail-anchored proteins factor 4) Enables chaperone binding activity. Involved in cytoplasmic sequestering of protein; maintenance of unfolded protein involved in ERAD pathway; and tail-anchored membrane protein insertion into ER membrane. Located in chromosome; cytosol; and nuclear lumen. Part of BAT3 complex. [provided by Alliance of Genome Resources, Apr 2022]

GET4 links:

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

SUN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 7-892317-C-T is Benign according to our data. Variant chr7-892317-C-T is described in ClinVar as Benign. ClinVar VariationId is 785870.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.483 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00185 (282/152340) while in subpopulation AMR AF = 0.0176 (270/15300). AF 95% confidence interval is 0.0159. There are 2 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GET4	NM_015949.3	MANE Select	c.645C>T	p.Val215Val	synonymous	Exon 6 of 9	NP_057033.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GET4	ENST00000265857.8	TSL:1 MANE Select	c.645C>T	p.Val215Val	synonymous	Exon 6 of 9	ENSP00000265857.3	Q7L5D6-1
GET4	ENST00000407192.5	TSL:1	c.486C>T	p.Val162Val	synonymous	Exon 5 of 8	ENSP00000385646.1	Q7L5D6-2
GET4	ENST00000919176.1		c.663C>T	p.Val221Val	synonymous	Exon 6 of 9	ENSP00000589235.1

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

283

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00456

AC:

1146

AN:

251190

AF XY:

0.00347

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.000963

AC:

1389

AN:

1442116

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

584

AN XY:

712636

show subpopulations

African (AFR)

AF:

0.000301

AC:

AN:

33188

American (AMR)

AF:

0.0298

AC:

1325

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.00

AC:

AN:

39036

South Asian (SAS)

AF:

0.00

AC:

AN:

85846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000110

AC:

AN:

1095376

Other (OTH)

AF:

0.000706

AC:

AN:

59454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00185

AC:

282

AN:

152340

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41588

American (AMR)

AF:

0.0176

AC:

270

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

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:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000523

Hom.:

Bravo

AF:

0.00322

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.7

(source)

DANN

Benign

0.90

PhyloP100

0.48

Mutation Taster

=85/15

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

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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