11-75743976-C-A

Variant names:

• chr11-75743976-C-A
• rs499974
• ENST00000770408.1:n.181+25773G>T

Variant summary

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

The ENST00000770408.1(ENSG00000300258):​n.181+25773G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,064 control chromosomes in the GnomAD database, including 4,216 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 0.22 (4216 hom., cov: 31)
• Consequence: ENSG00000300258 ENST00000770408.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 60 publications found

Genes affected

ENSG00000300258 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000770408.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000300258	ENST00000770408.1		n.181+25773G>T		intron	N/A
	ENSG00000300279	ENST00000770557.1		n.153-1528C>A		intron	N/A
	ENSG00000300279	ENST00000770558.1		n.-137C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33871 AN: 151946 Hom.: 4214 Cov.: 31

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.223 AC: 33899 AN: 152064 Hom.: 4216 Cov.: 31 AF XY: 0.222 AC XY: 16479 AN XY: 74338

African (AFR) AF: 0.339 AC: 14046 AN: 41470

American (AMR) AF: 0.160 AC: 2452 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3468

East Asian (EAS) AF: 0.259 AC: 1338 AN: 5164

South Asian (SAS) AF: 0.135 AC: 651 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2390 AN: 10574

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11716 AN: 67962

Other (OTH) AF: 0.200 AC: 421 AN: 2110

Alfa AF: 0.185 Hom.: 12243

Bravo AF: 0.225

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs499974; hg19: chr11-75455021;