1-72886346-C-A

Variant names:

• chr1-72886346-C-A
• rs6689491
• ENST00000445976.1:n.229+12421G>T

Variant summary

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

The ENST00000445976.1(ENSG00000225087):​n.229+12421G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,918 control chromosomes in the GnomAD database, including 18,405 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 0.49 (18405 hom., cov: 32)
• Consequence: ENSG00000225087 ENST00000445976.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 3 publications found

Genes affected

ENSG00000225087 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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
ENSG00000225087	ENST00000445976.1	n.229+12421G>T		intron_variant	Intron 2 of 4	3
ENSG00000225087	ENST00000654386.1	n.325+12421G>T		intron_variant	Intron 2 of 3
ENSG00000225087	ENST00000656766.1	n.474+12421G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74050 AN: 151800 Hom.: 18395 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.488 AC: 74116 AN: 151918 Hom.: 18405 Cov.: 32 AF XY: 0.491 AC XY: 36429 AN XY: 74258

African (AFR) AF: 0.528 AC: 21881 AN: 41426

American (AMR) AF: 0.420 AC: 6404 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3464

East Asian (EAS) AF: 0.720 AC: 3709 AN: 5150

South Asian (SAS) AF: 0.572 AC: 2755 AN: 4820

European-Finnish (FIN) AF: 0.441 AC: 4654 AN: 10554

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31349 AN: 67926

Other (OTH) AF: 0.496 AC: 1048 AN: 2114

Alfa AF: 0.327 Hom.: 850

Bravo AF: 0.485

Asia WGS AF: 0.627 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.74
PhyloP100		-0.60

Splicing

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

Other links and lift over

dbSNP: rs6689491; hg19: chr1-73352029;