ENST00000634644.1:n.952+22556T>C

Variant names:

• chr21-15444732-A-G
• rs1297265
• ENST00000634644.1:n.952+22556T>C

Variant summary

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

The ENST00000634644.1(ENSG00000229425):​n.952+22556T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,236 control chromosomes in the GnomAD database, including 14,587 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 0.43 (14578 hom., cov: 33)
  • Exomes 𝑓: 0.42 (9 hom.)
• Consequence: ENSG00000229425 ENST00000634644.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 41 publications found

Genes affected

ENSG00000229425 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634644.1. 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
	LOC101927745	NR_188234.1		n.-76T>C		upstream_gene	N/A
	LOC101927745	NR_188235.1		n.-76T>C		upstream_gene	N/A
	LOC101927745	NR_188236.1		n.-76T>C		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000229425	ENST00000634644.1	TSL:5	n.952+22556T>C		intron	N/A
	ENSG00000229425	ENST00000634708.1	TSL:5	n.423+33056T>C		intron	N/A
	ENSG00000229425	ENST00000654045.1		n.734-651T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65863 AN: 152010 Hom.: 14569 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.417 AC: 45 AN: 108 Hom.: 9 Cov.: 0 AF XY: 0.397 AC XY: 27 AN XY: 68

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.125 AC: 1 AN: 8

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.477 AC: 41 AN: 86

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.433 AC: 65910 AN: 152128 Hom.: 14578 Cov.: 33 AF XY: 0.426 AC XY: 31704 AN XY: 74370

African (AFR) AF: 0.468 AC: 19399 AN: 41486

American (AMR) AF: 0.431 AC: 6588 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3468

East Asian (EAS) AF: 0.185 AC: 957 AN: 5172

South Asian (SAS) AF: 0.360 AC: 1737 AN: 4826

European-Finnish (FIN) AF: 0.387 AC: 4102 AN: 10588

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30334 AN: 67978

Other (OTH) AF: 0.438 AC: 926 AN: 2114

Alfa AF: 0.426 Hom.: 42264

Bravo AF: 0.439

Asia WGS AF: 0.338 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.33
DANN	Benign	0.47
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs1297265; hg19: chr21-16817051;