rs7983774

Variant names:

• chr13-28390188-G-A
• rs7983774
• NM_002019.4:c.1661-84C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-28390188-G-A
• chr13-28390188-G-T

Variant summary

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

The NM_002019.4(FLT1):​c.1661-84C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,539,366 control chromosomes in the GnomAD database, including 65,420 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 0.27 (5927 hom., cov: 32)
  • Exomes 𝑓: 0.29 (59493 hom.)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 15 publications found

Genes affected

FLT1 (HGNC:3763): (fms related receptor tyrosine kinase 1) This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.1661-84C>T		intron	N/A	NP_002010.2
	FLT1	NM_001160030.2		c.1661-84C>T		intron	N/A	NP_001153502.1
	FLT1	NM_001159920.2		c.1661-84C>T		intron	N/A	NP_001153392.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.1661-84C>T		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.1661-84C>T		intron	N/A	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.1661-84C>T		intron	N/A	ENSP00000484039.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40776 AN: 151862 Hom.: 5922 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.288 AC: 399922 AN: 1387386 Hom.: 59493 AF XY: 0.289 AC XY: 199912 AN XY: 691646

African (AFR) AF: 0.174 AC: 5499 AN: 31650

American (AMR) AF: 0.175 AC: 7256 AN: 41398

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7675 AN: 25268

East Asian (EAS) AF: 0.399 AC: 15384 AN: 38526

South Asian (SAS) AF: 0.283 AC: 23126 AN: 81840

European-Finnish (FIN) AF: 0.406 AC: 17805 AN: 43866

Middle Eastern (MID) AF: 0.255 AC: 1431 AN: 5614

European-Non Finnish (NFE) AF: 0.287 AC: 304874 AN: 1061270

Other (OTH) AF: 0.291 AC: 16872 AN: 57954

GnomAD4 genome AF: 0.268 AC: 40796 AN: 151980 Hom.: 5927 Cov.: 32 AF XY: 0.271 AC XY: 20124 AN XY: 74268

African (AFR) AF: 0.179 AC: 7415 AN: 41440

American (AMR) AF: 0.213 AC: 3253 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2215 AN: 5172

South Asian (SAS) AF: 0.291 AC: 1401 AN: 4818

European-Finnish (FIN) AF: 0.402 AC: 4225 AN: 10512

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20380 AN: 67972

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.265 Hom.: 3004

Bravo AF: 0.250

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.39
PhyloP100		-0.28
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: rs7983774; hg19: chr13-28964325; COSMIC: COSV56740591;