1-47219911-C-T

Variant names:

• chr1-47219911-C-T
• rs777427139
• NM_001290403.2:c.805G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001290403.2(TAL1):​c.805G>A​(p.Gly269Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,494,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: TAL1 NM_001290403.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.851
• Publications: 0 publications found

Genes affected

TAL1 (HGNC:11556): (TAL bHLH transcription factor 1, erythroid differentiation factor) Enables several functions, including DNA-binding transcription factor activity; E-box binding activity; and histone deacetylase binding activity. Involved in several processes, including myeloid cell differentiation; positive regulation of cellular component organization; and positive regulation of erythrocyte differentiation. Located in chromatin and nucleoplasm. Part of transcription regulator complex. Implicated in acute lymphoblastic leukemia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008007526).
• BS2: High AC in GnomAd4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290403.2. 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
	TAL1	NM_001290403.2	MANE Select	c.805G>A	p.Gly269Ser	missense	Exon 5 of 5	NP_001277332.1	P17542-1
	TAL1	NM_001287347.2		c.805G>A	p.Gly269Ser	missense	Exon 5 of 5	NP_001274276.1	Q16509
	TAL1	NM_001290404.1		c.805G>A	p.Gly269Ser	missense	Exon 6 of 6	NP_001277333.1	P17542-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL1	ENST00000691006.1	MANE Select	c.805G>A	p.Gly269Ser	missense	Exon 5 of 5	ENSP00000510655.1	P17542-1
	TAL1	ENST00000294339.3	TSL:1	c.805G>A	p.Gly269Ser	missense	Exon 4 of 4	ENSP00000294339.3	P17542-1
	TAL1	ENST00000371884.6	TSL:1	c.805G>A	p.Gly269Ser	missense	Exon 5 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes AF: 0.000120 AC: 18 AN: 149836 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00409

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000447

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 23 AN: 141216 AF XY: 0.000173

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00305

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.000264

GnomAD4 exome AF: 0.000183 AC: 246 AN: 1344700 Hom.: 1 Cov.: 65 AF XY: 0.000204 AC XY: 134 AN XY: 658078

African (AFR) AF: 0.0000322 AC: 1 AN: 31032

American (AMR) AF: 0.0000301 AC: 1 AN: 33266

Ashkenazi Jewish (ASJ) AF: 0.00320 AC: 68 AN: 21274

East Asian (EAS) AF: 0.00 AC: 0 AN: 37014

South Asian (SAS) AF: 0.00 AC: 0 AN: 71390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3728

European-Non Finnish (NFE) AF: 0.000155 AC: 162 AN: 1045518

Other (OTH) AF: 0.000253 AC: 14 AN: 55444

GnomAD4 genome AF: 0.000120 AC: 18 AN: 149836 Hom.: 0 Cov.: 30 AF XY: 0.0000956 AC XY: 7 AN XY: 73188

African (AFR) AF: 0.0000246 AC: 1 AN: 40722

American (AMR) AF: 0.00 AC: 0 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00409 AC: 14 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5026

South Asian (SAS) AF: 0.00 AC: 0 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000447 AC: 3 AN: 67068

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.000480 Hom.: 1

Bravo AF: 0.000196

ExAC AF: 0.000133 AC: 15

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	0.074
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.087	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.85
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.15
Sift	Benign	0.13	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.28
MVP		0.70
MPC		0.70
ClinPred		0.015	T
GERP RS		1.3
Varity_R		0.029
gMVP		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777427139; hg19: chr1-47685583;