rs12374648

Variant names:

• chr6-151208234-A-G
• rs12374648
• ENST00000415477.1:n.66+20148T>C

Variant summary

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

The ENST00000415477.1(ENSG00000223598):​n.66+20148T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,960 control chromosomes in the GnomAD database, including 3,727 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 (3727 hom., cov: 31)
• Consequence: ENSG00000223598 ENST00000415477.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 3 publications found

Genes affected

ENSG00000223598 (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 (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102723831	NR_125868.1	n.77-10599T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000223598	ENST00000415477.1	n.66+20148T>C		intron_variant	Intron 1 of 4	5
ENSG00000223598	ENST00000772725.1	n.83-10599T>C		intron_variant	Intron 1 of 3
ENSG00000223598	ENST00000772726.1	n.61+20148T>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33290 AN: 151840 Hom.: 3727 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.219 AC: 33297 AN: 151960 Hom.: 3727 Cov.: 31 AF XY: 0.218 AC XY: 16199 AN XY: 74306

African (AFR) AF: 0.217 AC: 9011 AN: 41442

American (AMR) AF: 0.262 AC: 4000 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1850 AN: 5158

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1467 AN: 10594

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14168 AN: 67910

Other (OTH) AF: 0.233 AC: 490 AN: 2106

Alfa AF: 0.211 Hom.: 396

Bravo AF: 0.229

Asia WGS AF: 0.309 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs12374648; hg19: chr6-151529369;