chr2-21259420-G-A

Variant names:

• chr2-21259420-G-A
• rs10195618
• ENST00000435237.1:n.120+38126G>A

Variant summary

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

The ENST00000435237.1(ENSG00000231204):​n.120+38126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,174 control chromosomes in the GnomAD database, including 55,519 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 0.85 (55519 hom., cov: 32)
• Consequence: ENSG00000231204 ENST00000435237.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 6 publications found

Genes affected

ENSG00000231204 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374317	XR_002959373.2	n.136-4278G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000231204	ENST00000435237.1	n.120+38126G>A		intron_variant	Intron 1 of 5	3
ENSG00000231204	ENST00000457901.2	n.113-4273G>A		intron_variant	Intron 1 of 1	3
ENSG00000231204	ENST00000670105.1	n.256+521G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129483 AN: 152056 Hom.: 55511 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.851 AC: 129526 AN: 152174 Hom.: 55519 Cov.: 32 AF XY: 0.849 AC XY: 63143 AN XY: 74394

African (AFR) AF: 0.747 AC: 30998 AN: 41472

American (AMR) AF: 0.865 AC: 13228 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3063 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4855 AN: 5186

South Asian (SAS) AF: 0.895 AC: 4307 AN: 4814

European-Finnish (FIN) AF: 0.844 AC: 8943 AN: 10600

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61222 AN: 68024

Other (OTH) AF: 0.861 AC: 1816 AN: 2108

Alfa AF: 0.885 Hom.: 78631

Bravo AF: 0.847

Asia WGS AF: 0.912 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.41
PhyloP100		0.40

Splicing

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

Other links and lift over

dbSNP: rs10195618; hg19: chr2-21482292;