chr14-35363460-T-G

Variant names:

• chr14-35363460-T-G
• rs8016947
• ENST00000555024.1:n.61+108A>C

Variant summary

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

The ENST00000555024.1(ENSG00000258860):​n.61+108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,102 control chromosomes in the GnomAD database, including 27,302 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 0.60 (27295 hom., cov: 32)
  • Exomes 𝑓: 0.63 (7 hom.)
• Consequence: ENSG00000258860 ENST00000555024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 73 publications found

Genes affected

ENSG00000258860 (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 (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555024.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000258860	ENST00000555024.1	TSL:3	n.61+108A>C		intron	N/A
	ENSG00000258860	ENST00000723981.1		n.*2A>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90675 AN: 151952 Hom.: 27261 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.625 AC: 20 AN: 32 Hom.: 7 AF XY: 0.875 AC XY: 14 AN XY: 16

⚠️ 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: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.650 AC: 13 AN: 20

Other (OTH) AF: 0.750 AC: 6 AN: 8

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000662014), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.597 AC: 90770 AN: 152070 Hom.: 27295 Cov.: 32 AF XY: 0.597 AC XY: 44388 AN XY: 74330

African (AFR) AF: 0.631 AC: 26150 AN: 41474

American (AMR) AF: 0.694 AC: 10597 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2922 AN: 5166

South Asian (SAS) AF: 0.605 AC: 2917 AN: 4822

European-Finnish (FIN) AF: 0.570 AC: 6030 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38168 AN: 67968

Other (OTH) AF: 0.582 AC: 1231 AN: 2114

Alfa AF: 0.570 Hom.: 99692

Bravo AF: 0.609

Asia WGS AF: 0.601 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.43
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs8016947; hg19: chr14-35832666;