2-221695821-G-C

Variant names:

• chr2-221695821-G-C
• rs825280
• ENST00000757163.1:n.258-4267G>C

Variant summary

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

The ENST00000757163.1(ENSG00000234446):​n.258-4267G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,038 control chromosomes in the GnomAD database, including 60,153 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 0.88 (60153 hom., cov: 32)
• Consequence: ENSG00000234446 ENST00000757163.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 2 publications found

Genes affected

ENSG00000234446 (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 (NFE) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105373899	XR_001739234.1	n.358-4267G>C		intron_variant	Intron 4 of 8
LOC105373899	XR_001739235.1	n.321-4267G>C		intron_variant	Intron 3 of 6
LOC105373899	XR_923942.1	n.321-4267G>C		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000234446	ENST00000757163.1	n.258-4267G>C		intron_variant	Intron 2 of 3
ENSG00000234446	ENST00000757164.1	n.269-4267G>C		intron_variant	Intron 2 of 4
ENSG00000234446	ENST00000757165.1	n.325-4267G>C		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133755 AN: 151920 Hom.: 60138 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.955

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.880 AC: 133807 AN: 152038 Hom.: 60153 Cov.: 32 AF XY: 0.879 AC XY: 65328 AN XY: 74312

African (AFR) AF: 0.682 AC: 28273 AN: 41486

American (AMR) AF: 0.874 AC: 13320 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3349 AN: 3470

East Asian (EAS) AF: 0.826 AC: 4253 AN: 5150

South Asian (SAS) AF: 0.967 AC: 4671 AN: 4832

European-Finnish (FIN) AF: 0.935 AC: 9889 AN: 10572

Middle Eastern (MID) AF: 0.952 AC: 278 AN: 292

European-Non Finnish (NFE) AF: 0.985 AC: 66944 AN: 67978

Other (OTH) AF: 0.909 AC: 1919 AN: 2112

Alfa AF: 0.932 Hom.: 3300

Bravo AF: 0.864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs825280; hg19: chr2-222560541;