Genetic Variant CRCT1:p.Gly20Ser (chr1-152515441-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019060.3(CRCT1):c.58G>A(p.Gly20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00979 in 1,598,488 control chromosomes in the GnomAD database, including 1,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 512 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 495 hom. )

Consequence

CRCT1
NM_019060.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.802

Publications

14 publications found

Variant links:

Genes affected

CRCT1 (HGNC:29875): (cysteine rich C-terminal 1)

CRCT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012534857).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRCT1	NM_019060.3 link	c.58G>A	p.Gly20Ser	missense_variant	Exon 2 of 2	ENST00000368790.4	NP_061933.1	Q9UGL9
CRCT1	XM_011509656.3 link	c.58G>A	p.Gly20Ser	missense_variant	Exon 2 of 2		XP_011507958.1	Q9UGL9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRCT1	ENST00000368790.4 link	c.58G>A	p.Gly20Ser	missense_variant	Exon 2 of 2	1	NM_019060.3	ENSP00000357779.3		Q9UGL9

Frequencies

GnomAD3 genomes

AF:

0.0464

AC:

7065

AN:

152172

Hom.:

510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0130

AC:

2990

AN:

229668

AF XY:

0.00997

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.000222

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000549

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00592

AC:

8567

AN:

1446198

Hom.:

495

Cov.:

AF XY:

0.00540

AC XY:

3879

AN XY:

718690

show subpopulations

African (AFR)

AF:

0.165

AC:

5403

AN:

32782

American (AMR)

AF:

0.0140

AC:

605

AN:

43064

Ashkenazi Jewish (ASJ)

AF:

0.000197

AC:

AN:

25360

East Asian (EAS)

AF:

0.00

AC:

AN:

39368

South Asian (SAS)

AF:

0.00109

AC:

AN:

84434

European-Finnish (FIN)

AF:

0.0000406

AC:

AN:

49294

Middle Eastern (MID)

AF:

0.0260

AC:

132

AN:

5074

European-Non Finnish (NFE)

AF:

0.00140

AC:

1554

AN:

1107072

Other (OTH)

AF:

0.0130

AC:

774

AN:

59750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

418

835

1253

1670

2088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.0465

AC:

7075

AN:

152290

Hom.:

512

Cov.:

AF XY:

0.0442

AC XY:

3290

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.157

AC:

6526

AN:

41558

American (AMR)

AF:

0.0222

AC:

340

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00185

AC:

126

AN:

68028

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

310

620

930

1240

1550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0170

Hom.:

364

Bravo

AF:

0.0522

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.147

AC:

645

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.0151

AC:

1817

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.092

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

PhyloP100

0.80

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.068

Sift4G

Benign

0.54

Polyphen

0.13

Vest4

0.059

MPC

0.32

ClinPred

0.028

GERP RS

2.3

Varity_R

0.49

gMVP

0.022

Mutation Taster

=97/3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over