17-78325428-C-T

Variant names:

• chr17-78325428-C-T
• rs12449451
• ENST00000586321.1:n.60+9640C>T

Variant summary

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

The ENST00000586321.1(ENSG00000267737):​n.60+9640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 94,864 control chromosomes in the GnomAD database, including 5,552 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 0.42 (5552 hom., cov: 33)
• Consequence: ENSG00000267737 ENST00000586321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 1 publications found

Genes affected

ENSG00000267737 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371912	NR_188632.1	n.73+9640C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000267737	ENST00000586321.1	n.60+9640C>T		intron_variant	Intron 1 of 2	3
ENSG00000267737	ENST00000823930.1	n.38+9640C>T		intron_variant	Intron 1 of 1
ENSG00000267737	ENST00000823931.1	n.71+7440C>T		intron_variant	Intron 1 of 1
ENSG00000307142	ENST00000824249.1	n.*52C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.415 AC: 39348 AN: 94818 Hom.: 5554 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.384

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.415 AC: 39375 AN: 94864 Hom.: 5552 Cov.: 33 AF XY: 0.416 AC XY: 19189 AN XY: 46128

African (AFR) AF: 0.453 AC: 8408 AN: 18578

American (AMR) AF: 0.382 AC: 3419 AN: 8946

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 567 AN: 2362

East Asian (EAS) AF: 0.384 AC: 211 AN: 550

South Asian (SAS) AF: 0.303 AC: 699 AN: 2304

European-Finnish (FIN) AF: 0.455 AC: 3710 AN: 8158

Middle Eastern (MID) AF: 0.383 AC: 85 AN: 222

European-Non Finnish (NFE) AF: 0.416 AC: 21543 AN: 51778

Other (OTH) AF: 0.386 AC: 541 AN: 1402

Alfa AF: 0.206 Hom.: 581

Bravo AF: 0.245

Asia WGS AF: 0.130 AC: 435 AN: 3340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.025
DANN	Benign	0.77
PhyloP100		-3.3

Splicing

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

Other links and lift over

dbSNP: rs12449451; hg19: chr17-76321509;