rs6686424

Variant names:

• chr1-214023291-T-C
• rs6686424
• NM_001270616.2:c.2028+11576T>C

Variant summary

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

The NM_001270616.2(PROX1):​c.2028+11576T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 152,092 control chromosomes in the GnomAD database, including 1,651 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 0.094 (1651 hom., cov: 32)
• Consequence: PROX1 NM_001270616.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 3 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]

LINC02775 (HGNC:54294): (long intergenic non-protein coding RNA 2775)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1	NM_001270616.2	c.2028+11576T>C		intron_variant	Intron 4 of 4	ENST00000366958.9	NP_001257545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROX1	ENST00000366958.9	c.2028+11576T>C		intron_variant	Intron 4 of 4	1	NM_001270616.2	ENSP00000355925.4
PROX1	ENST00000435016.2	c.2028+11576T>C		intron_variant	Intron 4 of 4	1		ENSP00000400694.1
LINC02775	ENST00000729802.1	n.281-851A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14240 AN: 151982 Hom.: 1638 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0655

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

GnomAD4 genome AF: 0.0940 AC: 14302 AN: 152092 Hom.: 1651 Cov.: 32 AF XY: 0.0923 AC XY: 6864 AN XY: 74358

African (AFR) AF: 0.274 AC: 11358 AN: 41470

American (AMR) AF: 0.0428 AC: 654 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5178

South Asian (SAS) AF: 0.00623 AC: 30 AN: 4816

European-Finnish (FIN) AF: 0.0498 AC: 526 AN: 10558

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1429 AN: 68010

Other (OTH) AF: 0.0715 AC: 151 AN: 2112

Alfa AF: 0.0445 Hom.: 752

Bravo AF: 0.101

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.64
PhyloP100		-1.9
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: rs6686424; hg19: chr1-214196634;