rs4002422

Variant names:

• chr19-49044395-C-T
• rs4002422
• NM_033043.2:c.15+171C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_033043.2(CGB5):​c.15+171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 980,706 control chromosomes in the GnomAD database, including 6 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 0.0021 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00099 (6 hom.)
• Consequence: CGB5 NM_033043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 1 publications found

Genes affected

CGB5 (HGNC:16452): (chorionic gonadotropin subunit beta 5) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 5 subunit of chorionic gonadotropin (CG). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. CG is produced by the trophoblastic cells of the placenta and stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy. The beta subunit of CG is encoded by 6 genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 and contiguous with the luteinizing hormone beta subunit gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033043.2. 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
	CGB5	NM_033043.2	MANE Select	c.15+171C>T		intron	N/A	NP_149032.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB5	ENST00000301408.7	TSL:1 MANE Select	c.15+171C>T		intron	N/A	ENSP00000301408.5	P0DN86-1

Frequencies

GnomAD3 genomes AF: 0.00213 AC: 315 AN: 147950 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00409

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.000793

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00177

Gnomad OTH AF: 0.00339

GnomAD4 exome AF: 0.000991 AC: 825 AN: 832648 Hom.: 6 Cov.: 32 AF XY: 0.000988 AC XY: 380 AN XY: 384514

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

African (AFR) AF: 0.000709 AC: 11 AN: 15504

American (AMR) AF: 0.00 AC: 0 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 12 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3630

South Asian (SAS) AF: 0.000669 AC: 11 AN: 16454

European-Finnish (FIN) AF: 0.00362 AC: 1 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.000999 AC: 761 AN: 761746

Other (OTH) AF: 0.00106 AC: 29 AN: 27284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00213 AC: 316 AN: 148058 Hom.: 0 Cov.: 27 AF XY: 0.00206 AC XY: 149 AN XY: 72372

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

African (AFR) AF: 0.00408 AC: 154 AN: 37756

American (AMR) AF: 0.000792 AC: 12 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5148

South Asian (SAS) AF: 0.000627 AC: 3 AN: 4784

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00178 AC: 121 AN: 67876

Other (OTH) AF: 0.00335 AC: 7 AN: 2088

⚠️ 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: 0.00275 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.064
DANN	Benign	0.30
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4002422;

hg19: chr19-49547652;