17-63910252-G-C

Variant names:

• chr17-63910252-G-C
• rs61762513
• NM_022579.3:c.381C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_022579.3(CSHL1):​c.381C>G​(p.Thr127Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000627 in 1,614,144 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (2 hom.)
• Consequence: CSHL1 NM_022579.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.851
• Publications: 1 publications found

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]

ENSG00000303015 (HGNC:):

ACMG classification

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

• BP6: Variant 17-63910252-G-C is Benign according to our data. Variant chr17-63910252-G-C is described in ClinVar as Benign. ClinVar VariationId is 730144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022579.3. 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
	CSHL1	NM_022579.3	MANE Select	c.381C>G	p.Thr127Thr	synonymous	Exon 4 of 5	NP_072101.1	Q14406-1
	CSHL1	NM_022581.3		c.312C>G	p.Thr104Thr	synonymous	Exon 4 of 5	NP_072103.1	Q14406-2
	CSHL1	NM_001321069.2		c.264C>G	p.Thr88Thr	synonymous	Exon 4 of 5	NP_001307998.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSHL1	ENST00000309894.6	TSL:5 MANE Select	c.381C>G	p.Thr127Thr	synonymous	Exon 4 of 5	ENSP00000309524.5	Q14406-1
	CSHL1	ENST00000259003.14	TSL:1	c.195C>G	p.Thr65Thr	synonymous	Exon 4 of 5	ENSP00000259003.10	A0A0B4J1R0
	CSHL1	ENST00000346606.10	TSL:1	c.99C>G	p.Thr33Thr	synonymous	Exon 3 of 4	ENSP00000316360.10	Q14406-4

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 471 AN: 152184 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000887 AC: 223 AN: 251422 AF XY: 0.000714

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000370 AC: 541 AN: 1461842 Hom.: 2 Cov.: 84 AF XY: 0.000349 AC XY: 254 AN XY: 727226

African (AFR) AF: 0.0118 AC: 396 AN: 33460

American (AMR) AF: 0.000783 AC: 35 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112000

Other (OTH) AF: 0.000795 AC: 48 AN: 60390

GnomAD4 genome AF: 0.00309 AC: 471 AN: 152302 Hom.: 6 Cov.: 32 AF XY: 0.00312 AC XY: 232 AN XY: 74470

African (AFR) AF: 0.0108 AC: 451 AN: 41572

American (AMR) AF: 0.000850 AC: 13 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000268 Hom.: 0

Bravo AF: 0.00339

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.38
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61762513; hg19: chr17-61987612;