rs41522944

Variant names:

• chr9-127843193-G-A
• rs41522944
• NM_001114753.3:c.120C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-127843193-G-A
• chr9-127843193-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001114753.3(ENG):​c.120C>T​(p.Gly40Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,614,206 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 30)
  • Exomes 𝑓: 0.0052 (25 hom.)
• Consequence: ENG NM_001114753.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -1.03
• Publications: 1 publications found

Genes affected

ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

ENG Gene-Disease associations (from GenCC):

• telangiectasia, hereditary hemorrhagic, type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• hereditary hemorrhagic telangiectasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• juvenile polyposis syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 9-127843193-G-A is Benign according to our data. Variant chr9-127843193-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 237016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00341 (519/152330) while in subpopulation NFE AF = 0.00563 (383/68026). AF 95% confidence interval is 0.00516. There are 2 homozygotes in GnomAd4. There are 222 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 519 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114753.3. 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
	ENG	NM_001114753.3	MANE Select	c.120C>T	p.Gly40Gly	synonymous	Exon 2 of 15	NP_001108225.1	P17813-1
	ENG	NM_000118.4		c.120C>T	p.Gly40Gly	synonymous	Exon 2 of 14	NP_000109.1	Q5T9B9
	ENG	NM_001406715.1		c.120C>T	p.Gly40Gly	synonymous	Exon 2 of 8	NP_001393644.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENG	ENST00000373203.9	TSL:1 MANE Select	c.120C>T	p.Gly40Gly	synonymous	Exon 2 of 15	ENSP00000362299.4	P17813-1
	ENG	ENST00000344849.5	TSL:1	c.120C>T	p.Gly40Gly	synonymous	Exon 2 of 14	ENSP00000341917.3	P17813-2
	ENG	ENST00000714047.1		c.120C>T	p.Gly40Gly	synonymous	Exon 2 of 15	ENSP00000519338.1	A0AAQ5BHC4

Frequencies

GnomAD3 genomes AF: 0.00341 AC: 519 AN: 152212 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00563

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00322 AC: 809 AN: 251452 AF XY: 0.00318

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00535

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00523 AC: 7645 AN: 1461876 Hom.: 25 Cov.: 32 AF XY: 0.00503 AC XY: 3661 AN XY: 727238

African (AFR) AF: 0.000836 AC: 28 AN: 33480

American (AMR) AF: 0.00394 AC: 176 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 25 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00103 AC: 89 AN: 86258

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53406

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00633 AC: 7040 AN: 1112008

Other (OTH) AF: 0.00452 AC: 273 AN: 60396

GnomAD4 genome AF: 0.00341 AC: 519 AN: 152330 Hom.: 2 Cov.: 30 AF XY: 0.00298 AC XY: 222 AN XY: 74482

African (AFR) AF: 0.00125 AC: 52 AN: 41576

American (AMR) AF: 0.00477 AC: 73 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00563 AC: 383 AN: 68026

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00463 Hom.: 1

Bravo AF: 0.00353

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00616

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	not specified (4)
-	-	3	Telangiectasia, hereditary hemorrhagic, type 1 (3)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Hereditary hemorrhagic telangiectasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.3
DANN	Benign	0.86
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs41522944; hg19: chr9-130605472;