chr1-207899110-C-T

Variant names:

• chr1-207899110-C-T
• rs146237257
• NM_001025109.2:c.379G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 16/22 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -16 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 VariationId is 725461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025109.2. 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
	CD34	NM_001025109.2	MANE Select	c.379G>A	p.Val127Ile	missense	Exon 3 of 8	NP_001020280.1	P28906-1
	CD34	NM_001773.3		c.379G>A	p.Val127Ile	missense	Exon 3 of 8	NP_001764.1	P28906-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD34	ENST00000310833.12	TSL:1 MANE Select	c.379G>A	p.Val127Ile	missense	Exon 3 of 8	ENSP00000310036.7	P28906-1
	CD34	ENST00000356522.4	TSL:1	c.379G>A	p.Val127Ile	missense	Exon 3 of 8	ENSP00000348916.4	P28906-2
	CD34	ENST00000963933.1		c.442G>A	p.Val148Ile	missense	Exon 4 of 9	ENSP00000633992.1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152150 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00102 AC: 256 AN: 251490 AF XY: 0.00105

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 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.: 5 Cov.: 33 AF XY: 0.00191 AC XY: 1391 AN XY: 727246

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86258

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00235 AC: 2617 AN: 1112008

Other (OTH) AF: 0.00126 AC: 76 AN: 60396

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74466

African (AFR) AF: 0.000505 AC: 21 AN: 41552

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00206 AC: 140 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00110

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00233 AC: 20

ExAC AF: 0.00111 AC: 135

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00166

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.77	T
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	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.0080
Sift	Benign	0.60	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.050
MVP		0.28
MPC		0.15
ClinPred		0.00019	T
GERP RS		-2.1
Varity_R		0.022
gMVP		0.13
Mutation Taster		=98/2	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: rs146237257; hg19: chr1-208072455;