rs770352516

Variant names:

• chr10-125719818-C-A
• rs770352516
• NM_001202438.2:c.11C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-125719818-C-A
• chr10-125719818-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001202438.2(EDRF1):​c.11C>A​(p.Ala4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: EDRF1 NM_001202438.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.470
• Publications: 1 publications found

Genes affected

EDRF1 (HGNC:24640): (erythroid differentiation regulatory factor 1) This gene may play a role in erythroid cell differentiation. The encoded protein inhibits DNA binding of the erythroid transcription factor GATA-1 and may regulate the expression of alpha-globin and gamma-globin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

EDRF1-AS1 (HGNC:49501): (EDRF1 antisense RNA 1)

EDRF1-DT (HGNC:54128): (EDRF1 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051727295).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202438.2. 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
	EDRF1	NM_001202438.2	MANE Select	c.11C>A	p.Ala4Asp	missense	Exon 1 of 25	NP_001189367.1	Q3B7T1-1
	EDRF1	NM_015608.3		c.11C>A	p.Ala4Asp	missense	Exon 1 of 24	NP_056423.2
	EDRF1	NR_110857.2		n.110C>A		non_coding_transcript_exon	Exon 1 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDRF1	ENST00000356792.9	TSL:1 MANE Select	c.11C>A	p.Ala4Asp	missense	Exon 1 of 25	ENSP00000349244.4	Q3B7T1-1
	EDRF1	ENST00000368815.6	TSL:1	n.11C>A		non_coding_transcript_exon	Exon 1 of 25	ENSP00000357805.2	Q3B7T1-4
	EDRF1	ENST00000419769.6	TSL:1	n.11C>A		non_coding_transcript_exon	Exon 1 of 26	ENSP00000396544.2	Q3B7T1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458372 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725408

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110780

Other (OTH) AF: 0.00 AC: 0 AN: 60214

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000825 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.47
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.062
Sift	Uncertain	0.023	D
Sift4G	Benign	0.087	T
Polyphen		0.0090	B
Vest4		0.11
MutPred		0.099		Gain of loop (P = 0.0121)
MVP		0.43
MPC		0.62
ClinPred		0.10	T
GERP RS		2.3
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.14
Mutation Taster		=94/6	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: rs770352516; hg19: chr10-127408387;