17-63895108-A-G

Position:

chr17-63895108-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001317.6(CSH1):c.568T>C(p.Tyr190His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,611,712 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 2 hom., cov: 29)

Exomes 𝑓: 0.00054 ( 8 hom. )

Consequence

CSH1
NM_001317.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

CSH1 (HGNC:2440): (chorionic somatomammotropin hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones and plays an important role in growth control. The gene is located at the growth hormone locus on chromosome 17 along with four other related genes 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. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed mainly in the placenta and utilizes multiple transcription initiation sites. Expression of the identical mature proteins for chorionic somatomammotropin hormones 1 and 2 is upregulated during development, although the ratio of 1 to 2 increases by term. Mutations in this gene result in placental lactogen deficiency and Silver-Russell syndrome. [provided by RefSeq, Jul 2008]

CSH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02113849).

BP6

Variant 17-63895108-A-G is Benign according to our data. Variant chr17-63895108-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3269767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSH1	NM_001317.6 linkuse as main transcript	c.568T>C	p.Tyr190His	missense_variant	5/5	ENST00000316193.13	NP_001308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSH1	ENST00000316193.13 linkuse as main transcript	c.568T>C	p.Tyr190His	missense_variant	5/5	1	NM_001317.6	ENSP00000316416	P1

Frequencies

GnomAD3 genomes

AF:

0.000524

AC:

AN:

150882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000694

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000502

AC:

126

AN:

250888

Hom.:

AF XY:

0.000450

AC XY:

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000537

AC:

785

AN:

1460712

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

411

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.000334

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000596

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000523

AC:

AN:

151000

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.000692

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000780

Hom.:

ExAC

AF:

0.00126

AC:

153

EpiCase

AF:

0.000764

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.32

DEOGEN2

Uncertain

0.43

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-0.59

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.16

Sift

Benign

0.33

T;T;.

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.23

MVP

0.14

MPC

1.4

ClinPred

0.0035

GERP RS

-0.065

Varity_R

0.17

gMVP

0.29

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