1-214007378-A-G

Variant names:

• chr1-214007378-A-G
• rs3767844
• NM_001270616.2:c.1833+2106A>G

Variant summary

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

The NM_001270616.2(PROX1):​c.1833+2106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,108 control chromosomes in the GnomAD database, including 9,954 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 0.35 (9954 hom., cov: 33)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.1833+2106A>G		intron_variant	Intron 3 of 4	ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.1833+2106A>G		intron_variant	Intron 3 of 4	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.1833+2106A>G		intron_variant	Intron 3 of 4	1		ENSP00000400694.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53131 AN: 151990 Hom.: 9924 Cov.: 33

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.350 AC: 53223 AN: 152108 Hom.: 9954 Cov.: 33 AF XY: 0.350 AC XY: 26011 AN XY: 74362

African (AFR) AF: 0.468 AC: 19407 AN: 41468

American (AMR) AF: 0.430 AC: 6569 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1086 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1607 AN: 5172

South Asian (SAS) AF: 0.182 AC: 878 AN: 4830

European-Finnish (FIN) AF: 0.304 AC: 3215 AN: 10570

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19417 AN: 67988

Other (OTH) AF: 0.344 AC: 727 AN: 2112

Alfa AF: 0.328 Hom.: 2391

Bravo AF: 0.367

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.1
DANN	Benign	0.83
PhyloP100		0.37
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: rs3767844; hg19: chr1-214180721;