1-47219897-G-C

Variant names:

• chr1-47219897-G-C
• rs144117146
• NM_001290403.2:c.819C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001290403.2(TAL1):​c.819C>G​(p.Gly273Gly) 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 Lovd as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G273G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-47219897-G-C is Benign according to our data. Variant chr1-47219897-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAL1	NM_001290403.2	c.819C>G	p.Gly273Gly	synonymous_variant	Exon 5 of 5	ENST00000691006.1	NP_001277332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAL1	ENST00000691006.1	c.819C>G	p.Gly273Gly	synonymous_variant	Exon 5 of 5		NM_001290403.2	ENSP00000510655.1
TAL1	ENST00000294339.3	c.819C>G	p.Gly273Gly	synonymous_variant	Exon 4 of 4	1		ENSP00000294339.3
TAL1	ENST00000371884.6	c.819C>G	p.Gly273Gly	synonymous_variant	Exon 5 of 5	1		ENSP00000360951.1
TAL1	ENST00000459729.1	n.587C>G		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 471 AN: 145448 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00250

Gnomad AMI AF: 0.00231

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.00649

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00217

Gnomad OTH AF: 0.00248

GnomAD3 exomes AF: 0.0000107 AC: 2 AN: 186182 Hom.: 0 AF XY: 0.00000983 AC XY: 1 AN XY: 101686

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000608

Gnomad NFE exome AF: 0.0000121

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00286 AC: 3823 AN: 1335282 Hom.: 0 Cov.: 64 AF XY: 0.00279 AC XY: 1835 AN XY: 656846

Gnomad4 AFR exome AF: 0.00283

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00291

Gnomad4 EAS exome AF: 0.00259

Gnomad4 SAS exome AF: 0.000832

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00310

Gnomad4 OTH exome AF: 0.00335

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00328 AC: 477 AN: 145570 Hom.: 0 Cov.: 31 AF XY: 0.00344 AC XY: 244 AN XY: 70866

Gnomad4 AFR AF: 0.00257

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.0119

Gnomad4 SAS AF: 0.0138

Gnomad4 FIN AF: 0.00649

Gnomad4 NFE AF: 0.00217

Gnomad4 OTH AF: 0.00245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.83
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs144117146; hg19: chr1-47685569;