ENST00000400371.2:n.1985+7625T>C

Variant names:

• chr20-46448270-A-G
• rs446112
• ENST00000400371.2:n.1985+7625T>C

Variant summary

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

The ENST00000400371.2(ENSG00000293461):​n.1985+7625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,012 control chromosomes in the GnomAD database, including 14,251 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 0.40 (14251 hom., cov: 32)
• Consequence: ENSG00000293461 ENST00000400371.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• Publications: 3 publications found

Genes affected

ENSG00000293461 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000293461	ENST00000400371.2	n.1985+7625T>C		intron_variant	Intron 3 of 3	1
ENSG00000293461	ENST00000849666.1	n.357+9405T>C		intron_variant	Intron 2 of 2
ENSG00000293461	ENST00000849667.1	n.421+9327T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60677 AN: 151894 Hom.: 14201 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.400 AC: 60790 AN: 152012 Hom.: 14251 Cov.: 32 AF XY: 0.392 AC XY: 29158 AN XY: 74324

African (AFR) AF: 0.659 AC: 27306 AN: 41418

American (AMR) AF: 0.323 AC: 4931 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1631 AN: 5168

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4812

European-Finnish (FIN) AF: 0.186 AC: 1968 AN: 10592

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20926 AN: 67954

Other (OTH) AF: 0.381 AC: 804 AN: 2112

Alfa AF: 0.355 Hom.: 15613

Bravo AF: 0.423

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.73
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs446112; hg19: chr20-45076909;