6-87088186-T-C

Variant names:

• chr6-87088186-T-C
• rs6155
• NM_000735.4:c.15A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000735.4(CGA):​c.15A>G​(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,585,232 control chromosomes in the GnomAD database, including 835 homozygotes. 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 0.044 (259 hom., cov: 31)
  • Exomes 𝑓: 0.022 (576 hom.)
• Consequence: CGA NM_000735.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 6 publications found

Genes affected

CGA (HGNC:1885): (glycoprotein hormones, alpha polypeptide) The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The alpha subunits of these hormones are identical, however, their beta chains are unique and confer biological specificity. The protein encoded by this gene is the alpha subunit and belongs to the glycoprotein hormones alpha chain family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.278 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000735.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGA	NM_000735.4	MANE Select	c.15A>G	p.Arg5Arg	synonymous	Exon 2 of 4	NP_000726.1
	CGA	NM_001252383.2		c.15A>G	p.Arg5Arg	synonymous	Exon 2 of 5	NP_001239312.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGA	ENST00000627148.3	TSL:1 MANE Select	c.15A>G	p.Arg5Arg	synonymous	Exon 2 of 4	ENSP00000486024.1
	CGA	ENST00000610310.3	TSL:3	c.15A>G	p.Arg5Arg	synonymous	Exon 2 of 5	ENSP00000482232.1
	CGA	ENST00000630630.2	TSL:2	c.15A>G	p.Arg5Arg	synonymous	Exon 2 of 3	ENSP00000487300.1

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6650 AN: 149758 Hom.: 259 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0360

GnomAD2 exomes AF: 0.0246 AC: 5579 AN: 226892 AF XY: 0.0236

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.00969

Gnomad EAS exome AF: 0.0000604

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.0223

Gnomad OTH exome AF: 0.0164

GnomAD4 exome AF: 0.0220 AC: 31645 AN: 1435376 Hom.: 576 Cov.: 30 AF XY: 0.0222 AC XY: 15831 AN XY: 713690

African (AFR) AF: 0.117 AC: 3757 AN: 32216

American (AMR) AF: 0.0121 AC: 520 AN: 42876

Ashkenazi Jewish (ASJ) AF: 0.00859 AC: 218 AN: 25370

East Asian (EAS) AF: 0.0000770 AC: 3 AN: 38936

South Asian (SAS) AF: 0.0266 AC: 2195 AN: 82410

European-Finnish (FIN) AF: 0.0242 AC: 1270 AN: 52390

Middle Eastern (MID) AF: 0.0293 AC: 166 AN: 5666

European-Non Finnish (NFE) AF: 0.0202 AC: 22137 AN: 1096476

Other (OTH) AF: 0.0234 AC: 1379 AN: 59036

GnomAD4 genome AF: 0.0444 AC: 6659 AN: 149856 Hom.: 259 Cov.: 31 AF XY: 0.0434 AC XY: 3177 AN XY: 73208

African (AFR) AF: 0.110 AC: 4396 AN: 39864

American (AMR) AF: 0.0176 AC: 266 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3466

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5134

South Asian (SAS) AF: 0.0222 AC: 106 AN: 4766

European-Finnish (FIN) AF: 0.0210 AC: 218 AN: 10378

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0229 AC: 1557 AN: 67860

Other (OTH) AF: 0.0356 AC: 74 AN: 2076

Alfa AF: 0.0323 Hom.: 360

Bravo AF: 0.0474

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.5
DANN	Benign	0.48
PhyloP100		0.28
Mutation Taster		=99/1	polymorphism (auto)

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: rs6155; hg19: chr6-87797904; COSMIC: COSV63644476; COSMIC: COSV63644476;