6-87085541-A-T

Variant names:

• chr6-87085541-A-T
• rs6631
• NM_000735.4:c.*215T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000735.4(CGA):​c.*215T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 488,000 control chromosomes in the GnomAD database, including 41,747 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 0.40 (12414 hom., cov: 33)
  • Exomes 𝑓: 0.41 (29333 hom.)
• Consequence: CGA NM_000735.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGA	NM_000735.4	MANE Select	c.*215T>A		3_prime_UTR	Exon 4 of 4	NP_000726.1	P01215
	CGA	NM_001252383.2		c.*215T>A		3_prime_UTR	Exon 5 of 5	NP_001239312.1	A0A087WYZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGA	ENST00000627148.3	TSL:1 MANE Select	c.*215T>A		3_prime_UTR	Exon 4 of 4	ENSP00000486024.1	P01215
	CGA	ENST00000369582.6	TSL:5	c.*215T>A		3_prime_UTR	Exon 5 of 5	ENSP00000358595.3	A0A0R4J2F0
	CGA	ENST00000610310.3	TSL:3	c.*215T>A		downstream_gene	N/A	ENSP00000482232.1	A0A087WYZ4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60743 AN: 152040 Hom.: 12402 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.408 AC: 137031 AN: 335842 Hom.: 29333 Cov.: 2 AF XY: 0.414 AC XY: 73116 AN XY: 176778

African (AFR) AF: 0.384 AC: 3835 AN: 9980

American (AMR) AF: 0.560 AC: 7617 AN: 13598

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 4511 AN: 10196

East Asian (EAS) AF: 0.534 AC: 12239 AN: 22922

South Asian (SAS) AF: 0.523 AC: 17560 AN: 33602

European-Finnish (FIN) AF: 0.374 AC: 9440 AN: 25246

Middle Eastern (MID) AF: 0.420 AC: 602 AN: 1434

European-Non Finnish (NFE) AF: 0.367 AC: 73345 AN: 199578

Other (OTH) AF: 0.409 AC: 7882 AN: 19286

GnomAD4 genome AF: 0.400 AC: 60800 AN: 152158 Hom.: 12414 Cov.: 33 AF XY: 0.406 AC XY: 30182 AN XY: 74370

African (AFR) AF: 0.382 AC: 15863 AN: 41492

American (AMR) AF: 0.519 AC: 7942 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3472

East Asian (EAS) AF: 0.538 AC: 2783 AN: 5170

South Asian (SAS) AF: 0.521 AC: 2514 AN: 4828

European-Finnish (FIN) AF: 0.377 AC: 3989 AN: 10592

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24790 AN: 67996

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.377 Hom.: 1424

Bravo AF: 0.410

Asia WGS AF: 0.492 AC: 1708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.4
DANN	Benign	0.80
PhyloP100		2.6
Mutation Taster		=100/0	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: rs6631; hg19: chr6-87795259;