1-201123851-C-T

Variant names:

• chr1-201123851-C-T
• rs942703
• NM_001270601.2:c.-506+3233G>A

Variant summary

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

The NM_001270601.2(ASCL5):​c.-506+3233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,084 control chromosomes in the GnomAD database, including 5,558 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 0.26 (5558 hom., cov: 32)
• Consequence: ASCL5 NM_001270601.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 3 publications found

Genes affected

ASCL5 (HGNC:33169): (achaete-scute family bHLH transcription factor 5) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be part of RNA polymerase II transcription regulator complex and chromatin. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASCL5	NM_001270601.2	c.-506+3233G>A		intron_variant	Intron 1 of 1	ENST00000449188.3	NP_001257530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASCL5	ENST00000449188.3	c.-506+3233G>A		intron_variant	Intron 1 of 1	3	NM_001270601.2	ENSP00000472681.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39943 AN: 151966 Hom.: 5551 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 39957 AN: 152084 Hom.: 5558 Cov.: 32 AF XY: 0.268 AC XY: 19910 AN XY: 74334

African (AFR) AF: 0.249 AC: 10311 AN: 41466

American (AMR) AF: 0.346 AC: 5292 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3464

East Asian (EAS) AF: 0.498 AC: 2570 AN: 5162

South Asian (SAS) AF: 0.343 AC: 1651 AN: 4820

European-Finnish (FIN) AF: 0.245 AC: 2585 AN: 10566

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16099 AN: 67994

Other (OTH) AF: 0.284 AC: 599 AN: 2110

Alfa AF: 0.250 Hom.: 2711

Bravo AF: 0.270

Asia WGS AF: 0.415 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs942703; hg19: chr1-201092979; COSMIC: COSV71877135;