rs6446992

Variant names:

• chr4-74362655-G-A
• rs6446992
• ENST00000805841.1:n.191+2496C>T

Variant summary

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

The ENST00000805841.1(ENSG00000304732):​n.191+2496C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 151,972 control chromosomes in the GnomAD database, including 53,177 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 0.83 (53177 hom., cov: 30)
• Consequence: ENSG00000304732 ENST00000805841.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 1 publications found

Genes affected

ENSG00000304732 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377276	NR_188415.1	n.191+2496C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000304732	ENST00000805841.1	n.191+2496C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126772 AN: 151854 Hom.: 53120 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.835 AC: 126883 AN: 151972 Hom.: 53177 Cov.: 30 AF XY: 0.833 AC XY: 61898 AN XY: 74276

African (AFR) AF: 0.885 AC: 36695 AN: 41440

American (AMR) AF: 0.867 AC: 13250 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2940 AN: 3468

East Asian (EAS) AF: 0.716 AC: 3690 AN: 5154

South Asian (SAS) AF: 0.742 AC: 3581 AN: 4824

European-Finnish (FIN) AF: 0.815 AC: 8592 AN: 10540

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.814 AC: 55292 AN: 67960

Other (OTH) AF: 0.846 AC: 1786 AN: 2112

Alfa AF: 0.850 Hom.: 12235

Bravo AF: 0.840

Asia WGS AF: 0.745 AC: 2591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.49
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs6446992; hg19: chr4-75228372;