Variant rs139141452 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022579.3(CSHL1):c.640C>T(p.Arg214Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000159 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

CSHL1
NM_022579.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.94

Variant links:

Genes affected

CSHL1 (HGNC:2442): (chorionic somatomammotropin hormone like 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. Although the five genes share a remarkably high degree of sequence identity, they are expressed selectively in different tissues. This particular family member is expressed in placental villi, although it was originally thought to be a pseudogene. In fact, alternative splicing suggests that the majority of the transcripts would be unable to express a secreted protein. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

CSHL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSHL1	NM_022579.3 link	c.640C>T	p.Arg214Cys	missense_variant	Exon 5 of 5	ENST00000309894.6	NP_072101.1	Q14406-1I6L999

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSHL1	ENST00000309894.6 link	c.640C>T	p.Arg214Cys	missense_variant	Exon 5 of 5	5	NM_022579.3	ENSP00000309524.5		Q14406-1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000191

AC:

AN:

251444

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000107

AC:

156

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152262

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.000676

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

.;.;.;.;D

Eigen

Benign

0.18

Eigen_PC

Benign

0.0097

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.63

D;D;D;D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

3.3

.;.;.;.;M

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.7

D;.;D;D;D

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

D;.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

.;.;D;D;D

Vest4

0.95

MVP

0.87

MPC

0.22

ClinPred

0.23

GERP RS

2.6

Varity_R

0.57

gMVP

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over