Genetic Variant DRC8:p.Ile141Thr (chr1-245087293-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032328.4(DRC8):c.422T>C(p.Ile141Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000826 in 1,611,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

DRC8
NM_032328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

Publications

0 publications found

Variant links:

Genes affected

DRC8 (HGNC:28166): (EF-hand calcium binding domain 2) The gene encodes a protein that contains two EF-hand calcium-binding domains although its function has yet to be determined. Alternatively spliced transcripts have been observed. [provided by RefSeq, Mar 2014]

DRC8 links:

ENSG00000305254 (HGNC:):

ENSG00000305254 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030481607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032328.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRC8	NM_032328.4	MANE Select	c.422T>C	p.Ile141Thr	missense	Exon 8 of 8	NP_115704.1	Q5VUJ9-2
DRC8	NM_001290327.2		c.452T>C	p.Ile151Thr	missense	Exon 8 of 8	NP_001277256.1
DRC8	NM_001143943.1		c.373+3605T>C		intron	N/A	NP_001137415.1	Q5VUJ9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFCAB2	ENST00000366523.6	TSL:3 MANE Select	c.422T>C	p.Ile141Thr	missense	Exon 8 of 8	ENSP00000355480.1	Q5VUJ9-2
EFCAB2	ENST00000948553.1		c.548T>C	p.Ile183Thr	missense	Exon 8 of 8	ENSP00000618612.1
EFCAB2	ENST00000923178.1		c.422T>C	p.Ile141Thr	missense	Exon 7 of 7	ENSP00000593237.1

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000117

AC:

AN:

247778

AF XY:

0.0000969

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000521

AC:

AN:

1458770

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

725770

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

33354

American (AMR)

AF:

0.0000231

AC:

AN:

43204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111714

Other (OTH)

AF:

0.000116

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000374

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.000603

Hom.:

Bravo

AF:

0.000570

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

M_CAP

Benign

0.040

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.86

PhyloP100

6.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.30

Sift

Benign

0.17

Sift4G

Benign

0.70

Polyphen

0.029

Vest4

0.26

MVP

0.76

MPC

0.18

ClinPred

0.049

GERP RS

4.5

gMVP

0.43

Mutation Taster

=80/20

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