Genetic Variant CD34:p.Val127Ile (chr1-207899110-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001025109.2(CD34):c.379G>A(p.Val127Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,614,158 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 5 hom. )

Consequence

CD34
NM_001025109.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33

Variant links:

Genes affected

CD34 (HGNC:1662): (CD34 molecule) The protein encoded by this gene may play a role in the attachment of stem cells to the bone marrow extracellular matrix or to stromal cells. This single-pass membrane protein is highly glycosylated and phosphorylated by protein kinase C. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CD34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062966645).

BP6

Variant 1-207899110-C-T is Benign according to our data. Variant chr1-207899110-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 725461.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD34	NM_001025109.2 link	c.379G>A	p.Val127Ile	missense_variant	Exon 3 of 8	ENST00000310833.12	NP_001020280.1	P28906-1
CD34	NM_001773.3 link	c.379G>A	p.Val127Ile	missense_variant	Exon 3 of 8		NP_001764.1	P28906-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD34	ENST00000310833.12 link	c.379G>A	p.Val127Ile	missense_variant	Exon 3 of 8	1	NM_001025109.2	ENSP00000310036.7	P28906-1
CD34	ENST00000356522.4 link	c.379G>A	p.Val127Ile	missense_variant	Exon 3 of 8	1		ENSP00000348916.4	P28906-2
CD34	ENST00000485761.1 link	n.25G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00102

AC:

256

AN:

251490

Hom.:

AF XY:

0.00105

AC XY:

143

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00190

AC:

2774

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1391

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00235

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152268

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00111

AC:

135

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0070

DANN

Benign

0.58

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.18

T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.0080

Sift

Benign

0.60

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;B

Vest4

0.050

MVP

0.28

MPC

0.15

ClinPred

0.00019

GERP RS

-2.1

Varity_R

0.022

gMVP

0.13

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over