rs9977677

Variant names:

• chr21-36680485-G-A
• rs9977677
• ENST00000832352.1:n.108+18424C>T

Variant summary

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

The ENST00000832352.1(ENSG00000231324):​n.108+18424C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,916 control chromosomes in the GnomAD database, including 10,028 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 0.35 (10028 hom., cov: 31)
• Consequence: ENSG00000231324 ENST00000832352.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 1 publications found

Genes affected

ENSG00000231324 (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 (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369308	NR_188245.1	n.83+18424C>T		intron_variant	Intron 1 of 2
LOC105369308	NR_188246.1	n.83+18424C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000231324	ENST00000832352.1	n.108+18424C>T		intron_variant	Intron 1 of 2
ENSG00000231324	ENST00000832353.1	n.84+18424C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52539 AN: 151796 Hom.: 10026 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.346 AC: 52545 AN: 151916 Hom.: 10028 Cov.: 31 AF XY: 0.347 AC XY: 25797 AN XY: 74242

African (AFR) AF: 0.206 AC: 8535 AN: 41434

American (AMR) AF: 0.317 AC: 4842 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1251 AN: 5158

South Asian (SAS) AF: 0.263 AC: 1263 AN: 4810

European-Finnish (FIN) AF: 0.537 AC: 5659 AN: 10540

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28472 AN: 67924

Other (OTH) AF: 0.340 AC: 718 AN: 2110

Alfa AF: 0.371 Hom.: 2144

Bravo AF: 0.329

Asia WGS AF: 0.230 AC: 801 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	1.5
DANN	Benign	0.46
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs9977677; hg19: chr21-38052785;