rs2827312

Positions:

• chr21-22259356-G-T
• chrNW_003315968.2-163585-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444130.1(ENSG00000226043):​n.385+46543G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,954 control chromosomes in the GnomAD database, including 10,261 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 0.36 (10261 hom., cov: 32)
• Consequence: ENSG00000226043 ENST00000444130.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

Genes affected

ENSG00000226043 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107985508	XR_007067937.1	n.404+46543G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000226043	ENST00000444130.1	n.385+46543G>T		intron_variant		5
ENSG00000226043	ENST00000654607.1	n.404+46543G>T		intron_variant
ENSG00000226043	ENST00000667099.1	n.404+46543G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54906 AN: 151836 Hom.: 10266 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.361 AC: 54922 AN: 151954 Hom.: 10261 Cov.: 32 AF XY: 0.357 AC XY: 26537 AN XY: 74262

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.393

Alfa AF: 0.373 Hom.: 19251

Bravo AF: 0.367

Asia WGS AF: 0.191 AC: 665 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2827312; hg19: chr21-23631676;