chr17-63896132-G-A

Variant names:

• chr17-63896132-G-A
• rs747146179
• NM_001317.6:c.114C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001317.6(CSH1):​c.114C>T​(p.His38His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000011 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSH1 NM_001317.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 0 publications found

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]

ENSG00000303015 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.394 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSH1	NM_001317.6	MANE Select	c.114C>T	p.His38His	synonymous	Exon 2 of 5	NP_001308.1	P0DML2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSH1	ENST00000316193.13	TSL:1 MANE Select	c.114C>T	p.His38His	synonymous	Exon 2 of 5	ENSP00000316416.8	P0DML2
	CSH1	ENST00000329882.8	TSL:2	c.114C>T	p.His38His	synonymous	Exon 2 of 4	ENSP00000333268.8	A6NFB4
	CSH1	ENST00000453363.7	TSL:5	c.114C>T	p.His38His	synonymous	Exon 2 of 3	ENSP00000402517.2	B1A4H2

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 1 AN: 30232 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000255

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: 0.0000625 AC: 10 AN: 159914 AF XY: 0.0000579

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000359

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000911

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000115 AC: 8 AN: 697418 Hom.: 1 Cov.: 9 AF XY: 0.0000112 AC XY: 4 AN XY: 356516

African (AFR) AF: 0.00 AC: 0 AN: 13558

American (AMR) AF: 0.000169 AC: 4 AN: 23696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14398

East Asian (EAS) AF: 0.0000343 AC: 1 AN: 29128

South Asian (SAS) AF: 0.0000190 AC: 1 AN: 52608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2342

European-Non Finnish (NFE) AF: 0.00000404 AC: 2 AN: 495034

Other (OTH) AF: 0.00 AC: 0 AN: 32956

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000331 AC: 1 AN: 30232 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 14416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3252

American (AMR) AF: 0.000255 AC: 1 AN: 3924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 518

East Asian (EAS) AF: 0.00 AC: 0 AN: 778

South Asian (SAS) AF: 0.00 AC: 0 AN: 1220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 112

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16982

Other (OTH) AF: 0.00 AC: 0 AN: 384

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.39
PromoterAI		-0.0081	Neutral

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

Other links and lift over

dbSNP: rs747146179; hg19: chr17-61973492;