rs73004856

chr1-152515441-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/18 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CRCT1	NM_019060.3	c.58G>A	p.Gly20Ser	missense_variant	2/2	ENST00000368790.4
CRCT1	XM_011509656.3	c.58G>A	p.Gly20Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRCT1	ENST00000368790.4	c.58G>A	p.Gly20Ser	missense_variant	2/2	1	NM_019060.3	P1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7065 AN: 152172 Hom.: 510 Cov.: 32

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

GnomAD3 exomes AF: 0.0130 AC: 2990 AN: 229668 Hom.: 203 AF XY: 0.00997 AC XY: 1257 AN XY: 126088

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 SAS exome AF: 0.000838

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.: 32 AF XY: 0.00540 AC XY: 3879 AN XY: 718690

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.000197

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.0000406

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.0130

GnomAD4 genome AF: 0.0465 AC: 7075 AN: 152290 Hom.: 512 Cov.: 32 AF XY: 0.0442 AC XY: 3290 AN XY: 74468

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.00693 Hom.: 86

Bravo AF: 0.0522

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.147 AC: 645

ESP6500EA AF: 0.00256 AC: 22

ExAC AF: 0.0151 AC: 1817

Asia WGS AF: 0.0120 AC: 42 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	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	20
Dann	Benign	0.97
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.94	P
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.068
Sift4G	Benign	0.54	T
Polyphen		0.13	B
Vest4		0.059
MPC		0.32
ClinPred		0.028	T
GERP RS		2.3
Varity_R		0.49
gMVP		0.022

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

LitVar

Other links and lift over

dbSNP: rs73004856; hg19: chr1-152487917; COSMIC: COSV57501252; COSMIC: COSV57501252;