rs2646012

Variant names:

• chr4-99386631-G-C
• rs2646012
• ENST00000762194.1:n.378-3011C>G

Variant summary

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

The ENST00000762194.1(ENSG00000299279):​n.378-3011C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,174 control chromosomes in the GnomAD database, including 59,977 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 0.89 (59977 hom., cov: 31)
• Consequence: ENSG00000299279 ENST00000762194.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 2 publications found

Genes affected

ENSG00000299279 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC102723576	XR_001741777.2	n.388-3011C>G		intron_variant	Intron 3 of 3
LOC102723576	XR_427569.4	n.1285-3011C>G		intron_variant	Intron 3 of 3
LOC102723576	XR_939020.3	n.1285-3011C>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000299279	ENST00000762194.1	n.378-3011C>G		intron_variant	Intron 3 of 4
ENSG00000299279	ENST00000762195.1	n.250-3011C>G		intron_variant	Intron 3 of 4
ENSG00000299279	ENST00000762196.1	n.493-3011C>G		intron_variant	Intron 3 of 4
ENSG00000299279	ENST00000762197.1	n.250-3011C>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134746 AN: 152056 Hom.: 59928 Cov.: 31

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.886 AC: 134856 AN: 152174 Hom.: 59977 Cov.: 31 AF XY: 0.885 AC XY: 65842 AN XY: 74386

African (AFR) AF: 0.937 AC: 38911 AN: 41544

American (AMR) AF: 0.829 AC: 12659 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3470

East Asian (EAS) AF: 0.856 AC: 4426 AN: 5172

South Asian (SAS) AF: 0.934 AC: 4503 AN: 4820

European-Finnish (FIN) AF: 0.855 AC: 9049 AN: 10588

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59856 AN: 68002

Other (OTH) AF: 0.850 AC: 1791 AN: 2108

Alfa AF: 0.889 Hom.: 7498

Bravo AF: 0.882

Asia WGS AF: 0.833 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs2646012; hg19: chr4-100307788;