rs12221649

Variant names:

• chr11-114019631-T-C
• rs12221649
• ENST00000770045.1:n.226-15631T>C

Variant summary

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

The ENST00000770045.1(ENSG00000300211):​n.226-15631T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,286 control chromosomes in the GnomAD database, including 1,112 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 0.11 (1112 hom., cov: 33)
• Consequence: ENSG00000300211 ENST00000770045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 2 publications found

Genes affected

ENSG00000300211 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 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
ENSG00000300211	ENST00000770045.1	n.226-15631T>C		intron_variant	Intron 2 of 3
ENSG00000300211	ENST00000770046.1	n.140+4138T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16865 AN: 152168 Hom.: 1112 Cov.: 33

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.111 AC: 16860 AN: 152286 Hom.: 1112 Cov.: 33 AF XY: 0.113 AC XY: 8443 AN XY: 74456

African (AFR) AF: 0.0463 AC: 1924 AN: 41568

American (AMR) AF: 0.153 AC: 2337 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1015 AN: 5180

South Asian (SAS) AF: 0.133 AC: 644 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1262 AN: 10604

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8700 AN: 68018

Other (OTH) AF: 0.130 AC: 275 AN: 2116

Alfa AF: 0.120 Hom.: 957

Bravo AF: 0.111

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs12221649; hg19: chr11-113890353;