21-41557202-A-C

Variant names:

• chr21-41557202-A-C
• rs2838063
• XR_937738.1:n.1251+2095T>G

Variant summary

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

The XR_937738.1(LOC105372809):​n.1251+2095T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,182 control chromosomes in the GnomAD database, including 3,085 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 0.19 (3085 hom., cov: 33)
• Consequence: LOC105372809 XR_937738.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 2 publications found

Genes affected

LOC105372809 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372809	XR_937738.1	n.1251+2095T>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29210 AN: 152064 Hom.: 3088 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.192 AC: 29212 AN: 152182 Hom.: 3085 Cov.: 33 AF XY: 0.191 AC XY: 14192 AN XY: 74406

African (AFR) AF: 0.117 AC: 4866 AN: 41518

American (AMR) AF: 0.212 AC: 3234 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3472

East Asian (EAS) AF: 0.176 AC: 909 AN: 5178

South Asian (SAS) AF: 0.224 AC: 1080 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2072 AN: 10596

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15451 AN: 67994

Other (OTH) AF: 0.204 AC: 430 AN: 2112

Alfa AF: 0.221 Hom.: 6053

Bravo AF: 0.192

Asia WGS AF: 0.202 AC: 701 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	0.27
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs2838063; hg19: chr21-42929129;