chr14-63314010-C-T

Variant names:

• chr14-63314010-C-T
• rs728526
• NM_145171.4:c.205-894G>A

Variant summary

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

The NM_145171.4(GPHB5):​c.205-894G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,118 control chromosomes in the GnomAD database, including 1,336 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 0.12 (1336 hom., cov: 32)
• Consequence: GPHB5 NM_145171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 3 publications found

Genes affected

GPHB5 (HGNC:18055): (glycoprotein hormone subunit beta 5) GPHB5 is a cystine knot-forming polypeptide and a subunit of the dimeric glycoprotein hormone family (Hsu et al., 2002 [PubMed 12089349]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPHB5	NM_145171.4	c.205-894G>A		intron_variant	Intron 2 of 2	ENST00000621500.2	NP_660154.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPHB5	ENST00000621500.2	c.205-894G>A		intron_variant	Intron 2 of 2	3	NM_145171.4	ENSP00000478993.1
GPHB5	ENST00000314140.2	c.205-894G>A		intron_variant	Intron 1 of 1	1		ENSP00000479431.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18600 AN: 152000 Hom.: 1321 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18659 AN: 152118 Hom.: 1336 Cov.: 32 AF XY: 0.118 AC XY: 8780 AN XY: 74348

African (AFR) AF: 0.194 AC: 8043 AN: 41494

American (AMR) AF: 0.106 AC: 1616 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 274 AN: 3472

East Asian (EAS) AF: 0.127 AC: 659 AN: 5170

South Asian (SAS) AF: 0.0532 AC: 256 AN: 4814

European-Finnish (FIN) AF: 0.0519 AC: 549 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6886 AN: 67988

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.106 Hom.: 1208

Bravo AF: 0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
PhyloP100		0.048

Splicing

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

Other links and lift over

dbSNP: rs728526; hg19: chr14-63780723;