Variant 4-71756884-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000583.4(GC):c.862A>G(p.Asn288Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,613,318 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 8 hom. )

Consequence

GC
NM_000583.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.541

Variant links:

Genes affected

GC (HGNC:4187): (GC vitamin D binding protein) The protein encoded by this gene belongs to the albumin gene family. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

GC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008902758).

BP6

Variant 4-71756884-T-C is Benign according to our data. Variant chr4-71756884-T-C is described in ClinVar as [Benign]. Clinvar id is 791393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GC	NM_000583.4 linkuse as main transcript	c.862A>G	p.Asn288Asp	missense_variant	8/13	ENST00000273951.13
GC	NM_001204307.1 linkuse as main transcript	c.919A>G	p.Asn307Asp	missense_variant	9/14
GC	NM_001204306.1 linkuse as main transcript	c.862A>G	p.Asn288Asp	missense_variant	9/14
GC	XM_006714177.3 linkuse as main transcript	c.862A>G	p.Asn288Asp	missense_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13 linkuse as main transcript	c.862A>G	p.Asn288Asp	missense_variant	8/13	1	NM_000583.4	P1	P02774-1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00169

AC:

424

AN:

251190

Hom.:

AF XY:

0.00188

AC XY:

255

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00192

AC:

2801

AN:

1461000

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1442

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00267

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00152

AC:

232

AN:

152318

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00156

AC:

189

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.5

DANN

Benign

0.73

DEOGEN2

Benign

0.17

T;.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.0089

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.10

.;.;B

Vest4

0.22

MVP

0.35

MPC

0.057

ClinPred

0.015

GERP RS

1.3

Varity_R

0.23

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over