chr19-49035873-C-G

Variant names:

• chr19-49035873-C-G
• rs574589925
• NM_033377.2:c.205G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_033377.2(CGB1):​c.205G>C​(p.Ala69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 25)
  • Exomes 𝑓: 0.0060 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: CGB1 NM_033377.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281
• Publications: 2 publications found

Genes affected

CGB1 (HGNC:16721): (chorionic gonadotropin subunit beta 1) The beta subunit of chorionic gonadotropin (CGB) is encoded by six highly homologous and structurally similar genes that are arranged in tandem and inverted pairs on chromosome 19q13.3, and contiguous with the luteinizing hormone beta (LHB) subunit gene. The CGB genes are primarily distinguished by differences in the 5' untranscribed region. This gene was originally thought to be one of the two pseudogenes (CGB1 and CGB2) of CGB subunit, however, detection of CGB1 and CGB2 transcripts in vivo, and their presence on the polysomes, suggested that these transcripts are translated. To date, a protein product corresponding to CGB1 has not been isolated. The deduced sequence of the hypothetical protein of 132 aa does not share any similarity with that of functional CGB subunits (PMID:8954017). However, a 155 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits. [provided by RefSeq, Jul 2008]

ENSG00000267335 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006509602).
• BP6: Variant 19-49035873-C-G is Benign according to our data. Variant chr19-49035873-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2650232.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033377.2. 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
	CGB1	NM_033377.2	MANE Select	c.205G>C	p.Ala69Pro	missense	Exon 3 of 3	NP_203695.2	A6NKQ9-2
	CGB1	NM_001382421.1		c.169G>C	p.Ala57Pro	missense	Exon 3 of 3	NP_001369350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB1	ENST00000301407.8	TSL:1 MANE Select	c.205G>C	p.Ala69Pro	missense	Exon 3 of 3	ENSP00000301407.6	A6NKQ9-2
	ENSG00000267335	ENST00000591656.1	TSL:2	c.-28+653G>C		intron	N/A	ENSP00000466140.1	K7ELM3
	ENSG00000267335	ENST00000604577.1	TSL:1	c.9+830G>C		intron	N/A	ENSP00000474022.1	S4R385

Frequencies

GnomAD3 genomes AF: 0.00394 AC: 576 AN: 146314 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.000957

Gnomad AMI AF: 0.00225

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00178

Gnomad FIN AF: 0.00119

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00631

Gnomad OTH AF: 0.00408

GnomAD2 exomes AF: 0.00420 AC: 449 AN: 106988 AF XY: 0.00432

Gnomad AFR exome AF: 0.000469

Gnomad AMR exome AF: 0.00435

Gnomad ASJ exome AF: 0.000207

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00210

Gnomad NFE exome AF: 0.00720

Gnomad OTH exome AF: 0.00783

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00596 AC: 7717 AN: 1295774 Hom.: 23 Cov.: 26 AF XY: 0.00587 AC XY: 3754 AN XY: 640016

African (AFR) AF: 0.000728 AC: 21 AN: 28846

American (AMR) AF: 0.00466 AC: 163 AN: 34980

Ashkenazi Jewish (ASJ) AF: 0.000439 AC: 10 AN: 22754

East Asian (EAS) AF: 0.00 AC: 0 AN: 35764

South Asian (SAS) AF: 0.00160 AC: 121 AN: 75468

European-Finnish (FIN) AF: 0.00131 AC: 49 AN: 37368

Middle Eastern (MID) AF: 0.000526 AC: 2 AN: 3802

European-Non Finnish (NFE) AF: 0.00706 AC: 7081 AN: 1002394

Other (OTH) AF: 0.00496 AC: 270 AN: 54398

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00393 AC: 576 AN: 146428 Hom.: 1 Cov.: 25 AF XY: 0.00386 AC XY: 275 AN XY: 71232

African (AFR) AF: 0.000954 AC: 37 AN: 38796

American (AMR) AF: 0.00595 AC: 88 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5054

South Asian (SAS) AF: 0.00178 AC: 8 AN: 4484

European-Finnish (FIN) AF: 0.00119 AC: 12 AN: 10110

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

European-Non Finnish (NFE) AF: 0.00631 AC: 420 AN: 66598

Other (OTH) AF: 0.00404 AC: 8 AN: 1982

Alfa AF: 0.00356 Hom.: 1

Bravo AF: 0.00413

ExAC AF: 0.00173 AC: 153

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.3
DANN	Benign	0.39
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00058	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0065	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.28
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.063
Sift	Benign	1.0	T
Sift4G	Benign	0.91	T
Polyphen		0.0010	B
Vest4		0.17
MVP		0.040
MPC		1.5
ClinPred		0.0027	T
GERP RS		-0.62
gMVP		0.27
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs574589925; hg19: chr19-49539130; COSMIC: COSV106097645; COSMIC: COSV106097645;