1-47219924-A-G

Variant names:

• chr1-47219924-A-G
• rs1403207816
• NM_001290403.2:c.792T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001290403.2(TAL1):​c.792T>C​(p.Ala264Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A264A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.151 with no splicing effect.

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.792T>C	p.Ala264Ala	synonymous	Exon 5 of 5	NP_001277332.1	P17542-1
	TAL1	NM_001287347.2		c.792T>C	p.Ala264Ala	synonymous	Exon 5 of 5	NP_001274276.1	Q16509
	TAL1	NM_001290404.1		c.792T>C	p.Ala264Ala	synonymous	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.792T>C	p.Ala264Ala	synonymous	Exon 5 of 5	ENSP00000510655.1	P17542-1
	TAL1	ENST00000294339.3	TSL:1	c.792T>C	p.Ala264Ala	synonymous	Exon 4 of 4	ENSP00000294339.3	P17542-1
	TAL1	ENST00000371884.6	TSL:1	c.792T>C	p.Ala264Ala	synonymous	Exon 5 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000229 AC: 1 AN: 435940 Hom.: 0 Cov.: 13 AF XY: 0.00000449 AC XY: 1 AN XY: 222812

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11612

American (AMR) AF: 0.00 AC: 0 AN: 19834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7474

East Asian (EAS) AF: 0.00 AC: 0 AN: 12286

South Asian (SAS) AF: 0.00 AC: 0 AN: 45974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1240

European-Non Finnish (NFE) AF: 0.00000333 AC: 1 AN: 300014

Other (OTH) AF: 0.00 AC: 0 AN: 17822

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.47
PhyloP100		0.15
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1403207816; hg19: chr1-47685596;