Variant chr9-110496872-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_153366.4(SVEP1):c.1743A>C(p.Gln581His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,557,606 control chromosomes in the GnomAD database, including 10,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1441 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9342 hom. )

Consequence

SVEP1
NM_153366.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00200

Variant links:

Genes affected

SVEP1 (HGNC:15985): (sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1) Predicted to enable calcium ion binding activity and chromatin binding activity. Predicted to be involved in epidermis development and lymph vessel morphogenesis. Predicted to act upstream of or within several processes, including Tie signaling pathway; lymph circulation; and lymph vessel development. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SVEP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014695525).

BP6

Variant 9-110496872-T-G is Benign according to our data. Variant chr9-110496872-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVEP1	NM_153366.4 linkuse as main transcript	c.1743A>C	p.Gln581His	missense_variant	8/48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6 linkuse as main transcript	c.1743A>C	p.Gln581His	missense_variant	8/48	5	NM_153366.4	ENSP00000363593	P1	Q4LDE5-1
SVEP1	ENST00000374461.1 linkuse as main transcript	c.1743A>C	p.Gln581His	missense_variant	8/14	1		ENSP00000363585		Q4LDE5-2
SVEP1	ENST00000467821.1 linkuse as main transcript	n.1162A>C		non_coding_transcript_exon_variant	7/26	2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19724

AN:

152128

Hom.:

1440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0412

Gnomad FIN

AF:

0.0910

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.0962

AC:

16293

AN:

169348

Hom.:

1017

AF XY:

0.0948

AC XY:

8457

AN XY:

89170

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.0705

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.000895

Gnomad SAS exome

AF:

0.0477

Gnomad FIN exome

AF:

0.0907

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.109

AC:

153445

AN:

1405360

Hom.:

9342

Cov.:

AF XY:

0.108

AC XY:

74944

AN XY:

693612

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0772

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.000514

Gnomad4 SAS exome

AF:

0.0494

Gnomad4 FIN exome

AF:

0.0892

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.130

AC:

19731

AN:

152246

Hom.:

1441

Cov.:

AF XY:

0.126

AC XY:

9380

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0410

Gnomad4 FIN

AF:

0.0910

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.117

Hom.:

2493

Bravo

AF:

0.137

TwinsUK

AF:

0.106

AC:

392

ALSPAC

AF:

0.109

AC:

419

ESP6500AA

AF:

0.181

AC:

687

ESP6500EA

AF:

0.116

AC:

951

ExAC

AF:

0.0703

AC:

7776

Asia WGS

AF:

0.0330

AC:

116

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M;M

MutationTaster

Benign

0.96

P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

D;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0050

D;.;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0, 0.028

.;D;B

Vest4

0.055

MutPred

0.23

Loss of catalytic residue at Q581 (P = 0.0581);Loss of catalytic residue at Q581 (P = 0.0581);Loss of catalytic residue at Q581 (P = 0.0581);

MPC

0.096

ClinPred

0.067

GERP RS

0.97

Varity_R

0.49

gMVP

0.33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over