16-12614351-C-T

Variant names:

• chr16-12614351-C-T
• rs1560104
• ENST00000615100.1:n.-100C>T

Variant summary

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

The ENST00000615100.1(ENSG00000274834):​n.-100C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,910 control chromosomes in the GnomAD database, including 15,637 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 0.43 (15637 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENSG00000274834 ENST00000615100.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 13 publications found

Genes affected

ENSG00000274834 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000274834	ENST00000615100.1	n.-100C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64985 AN: 151790 Hom.: 15614 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.428 AC: 65059 AN: 151908 Hom.: 15637 Cov.: 32 AF XY: 0.427 AC XY: 31682 AN XY: 74192

African (AFR) AF: 0.637 AC: 26384 AN: 41422

American (AMR) AF: 0.442 AC: 6741 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3468

East Asian (EAS) AF: 0.685 AC: 3538 AN: 5168

South Asian (SAS) AF: 0.425 AC: 2050 AN: 4818

European-Finnish (FIN) AF: 0.315 AC: 3307 AN: 10510

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20564 AN: 67948

Other (OTH) AF: 0.411 AC: 868 AN: 2110

Alfa AF: 0.356 Hom.: 34004

Bravo AF: 0.451

Asia WGS AF: 0.567 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs1560104; hg19: chr16-12708208;