rs3767848

Variant names:

• chr1-214000497-G-A
• rs3767848
• NM_001270616.2:c.1725+2237G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-214000497-G-A
• chr1-214000497-G-C
• chr1-214000497-G-T

Variant summary

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

The NM_001270616.2(PROX1):​c.1725+2237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,012 control chromosomes in the GnomAD database, including 8,696 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 0.32 (8696 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 11 publications found

Genes affected

PROX1 (HGNC:9459): (prospero homeobox 1) The protein encoded by this gene is a member of the homeobox transcription factor family. Members of this family contain a homeobox domain that consists of a 60-amino acid helix-turn-helix structure that binds DNA and RNA. The protein encoded by this gene is conserved across vertebrates and may play an essential role during development. Altered levels of this protein have been reported in cancers of different organs, such as colon, brain, blood, breast, pancreas, liver and esophagus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

PROX1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270616.2. 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
	PROX1	NM_001270616.2	MANE Select	c.1725+2237G>A		intron	N/A	NP_001257545.1	Q92786
	PROX1	NM_002763.5		c.1725+2237G>A		intron	N/A	NP_002754.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROX1	ENST00000366958.9	TSL:1 MANE Select	c.1725+2237G>A		intron	N/A	ENSP00000355925.4	Q92786
	PROX1	ENST00000435016.2	TSL:1	c.1725+2237G>A		intron	N/A	ENSP00000400694.1	Q92786
	PROX1	ENST00000881021.1		c.1725+2237G>A		intron	N/A	ENSP00000551080.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49284 AN: 151894 Hom.: 8667 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.325 AC: 49368 AN: 152012 Hom.: 8696 Cov.: 32 AF XY: 0.327 AC XY: 24270 AN XY: 74312

African (AFR) AF: 0.444 AC: 18381 AN: 41438

American (AMR) AF: 0.404 AC: 6174 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3464

East Asian (EAS) AF: 0.314 AC: 1625 AN: 5174

South Asian (SAS) AF: 0.165 AC: 793 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3452 AN: 10554

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17193 AN: 67970

Other (OTH) AF: 0.310 AC: 652 AN: 2106

Alfa AF: 0.281 Hom.: 8231

Bravo AF: 0.340

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.044
DANN	Benign	0.75
PhyloP100		-2.4
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: rs3767848; hg19: chr1-214173840;