1-47219924-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001290403.2(TAL1):​c.792T>G​(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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.096 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-47219924-A-C is Benign according to our data. Variant chr1-47219924-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3034085.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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>G	p.Ala264Ala	synonymous	Exon 5 of 5	NP_001277332.1	P17542-1
	TAL1	NM_001287347.2		c.792T>G	p.Ala264Ala	synonymous	Exon 5 of 5	NP_001274276.1	Q16509
	TAL1	NM_001290404.1		c.792T>G	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>G	p.Ala264Ala	synonymous	Exon 5 of 5	ENSP00000510655.1	P17542-1
	TAL1	ENST00000294339.3	TSL:1	c.792T>G	p.Ala264Ala	synonymous	Exon 4 of 4	ENSP00000294339.3	P17542-1
	TAL1	ENST00000371884.6	TSL:1	c.792T>G	p.Ala264Ala	synonymous	Exon 5 of 5	ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 4190 AN: 43556 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0100

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.00344 AC: 372 AN: 108018 AF XY: 0.00317

Gnomad AFR exome AF: 0.000122

Gnomad AMR exome AF: 0.000507

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.000870

Gnomad OTH exome AF: 0.00105

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00306 AC: 1259 AN: 411940 Hom.: 0 Cov.: 13 AF XY: 0.00298 AC XY: 625 AN XY: 209556

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

African (AFR) AF: 0.0000880 AC: 1 AN: 11364

American (AMR) AF: 0.000154 AC: 3 AN: 19498

Ashkenazi Jewish (ASJ) AF: 0.000142 AC: 1 AN: 7054

East Asian (EAS) AF: 0.00 AC: 0 AN: 11934

South Asian (SAS) AF: 0.00120 AC: 49 AN: 40734

European-Finnish (FIN) AF: 0.0644 AC: 1126 AN: 17486

Middle Eastern (MID) AF: 0.00172 AC: 2 AN: 1166

European-Non Finnish (NFE) AF: 0.000241 AC: 69 AN: 285844

Other (OTH) AF: 0.000474 AC: 8 AN: 16860

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0962 AC: 4193 AN: 43598 Hom.: 0 Cov.: 0 AF XY: 0.0861 AC XY: 1892 AN XY: 21982

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

African (AFR) AF: 0.0957 AC: 1124 AN: 11742

American (AMR) AF: 0.0545 AC: 286 AN: 5250

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 119 AN: 954

East Asian (EAS) AF: 0.0183 AC: 20 AN: 1092

South Asian (SAS) AF: 0.0525 AC: 61 AN: 1162

European-Finnish (FIN) AF: 0.0586 AC: 180 AN: 3074

Middle Eastern (MID) AF: 0.0111 AC: 1 AN: 90

European-Non Finnish (NFE) AF: 0.119 AC: 2305 AN: 19384

Other (OTH) AF: 0.117 AC: 76 AN: 652

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TAL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.47
PhyloP100		0.15
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;