chr1-207888710-C-T

Variant names:

• chr1-207888710-C-T
• rs146829371
• NM_001025109.2:c.944G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001025109.2(CD34):​c.944G>A​(p.Arg315His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,614,086 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: CD34 NM_001025109.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18660119).

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.944G>A	p.Arg315His	missense	Exon 7 of 8	NP_001020280.1	P28906-1
	CD34	NM_001773.3		c.944G>A	p.Arg315His	missense	Exon 7 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.944G>A	p.Arg315His	missense	Exon 7 of 8	ENSP00000310036.7	P28906-1
	CD34	ENST00000356522.4	TSL:1	c.944G>A	p.Arg315His	missense	Exon 7 of 8	ENSP00000348916.4	P28906-2
	CD34	ENST00000367036.7	TSL:1	c.470G>A	p.Arg157His	missense	Exon 4 of 5	ENSP00000356003.3	Q5JTA5

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000195 AC: 49 AN: 251380 AF XY: 0.000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000169 AC: 247 AN: 1461864 Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 127 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 55 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.000117 AC: 130 AN: 1111998

Other (OTH) AF: 0.000364 AC: 22 AN: 60396

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7 AN XY: 74362

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.29
MVP		0.76
MPC		0.23
ClinPred		0.67	D
GERP RS		4.5
Varity_R		0.51
gMVP		0.53
Mutation Taster		=77/23	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: rs146829371; hg19: chr1-208062055;