rs7534271

Variant names:

• chr1-47228309-C-G
• rs7534271
• ENST00000422216.1:n.1595C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422216.1(ENSG00000226252):​n.1595C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 177,046 control chromosomes in the GnomAD database, including 22,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (19614 hom., cov: 32)
  • Exomes 𝑓: 0.45 (3301 hom.)
• Consequence: ENSG00000226252 ENST00000422216.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 5 publications found

Genes affected

ENSG00000226252 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422216.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL1	NM_001290403.2	MANE Select	c.-2+887G>C		intron	N/A	NP_001277332.1
	TAL1	NM_001287347.2		c.-2+887G>C		intron	N/A	NP_001274276.1
	TAL1	NM_001290404.1		c.-2+887G>C		intron	N/A	NP_001277333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000226252	ENST00000422216.1	TSL:1	n.1595C>G		non_coding_transcript_exon	Exon 2 of 2
	TAL1	ENST00000691006.1	MANE Select	c.-2+887G>C		intron	N/A	ENSP00000510655.1
	TAL1	ENST00000294339.3	TSL:1	c.-2+887G>C		intron	N/A	ENSP00000294339.3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72981 AN: 151906 Hom.: 19593 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.449 AC: 11233 AN: 25020 Hom.: 3301 Cov.: 0 AF XY: 0.453 AC XY: 5186 AN XY: 11446

African (AFR) AF: 0.309 AC: 249 AN: 806

American (AMR) AF: 0.467 AC: 252 AN: 540

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 1028 AN: 1588

East Asian (EAS) AF: 0.00241 AC: 13 AN: 5394

South Asian (SAS) AF: 0.388 AC: 83 AN: 214

European-Finnish (FIN) AF: 0.250 AC: 3 AN: 12

Middle Eastern (MID) AF: 0.671 AC: 102 AN: 152

European-Non Finnish (NFE) AF: 0.594 AC: 8495 AN: 14312

Other (OTH) AF: 0.503 AC: 1008 AN: 2002

GnomAD4 genome AF: 0.480 AC: 73036 AN: 152026 Hom.: 19614 Cov.: 32 AF XY: 0.478 AC XY: 35484 AN XY: 74310

African (AFR) AF: 0.299 AC: 12401 AN: 41476

American (AMR) AF: 0.441 AC: 6731 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2210 AN: 3468

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5174

South Asian (SAS) AF: 0.466 AC: 2244 AN: 4814

European-Finnish (FIN) AF: 0.632 AC: 6664 AN: 10544

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40988 AN: 67972

Other (OTH) AF: 0.504 AC: 1064 AN: 2112

Alfa AF: 0.551 Hom.: 3009

Bravo AF: 0.455

Asia WGS AF: 0.270 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.46
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs7534271; hg19: chr1-47693981;