4-144509145-T-C

Variant names:

• chr4-144509145-T-C
• rs6827794
• ENST00000649263.1:n.328-93167A>G

Variant summary

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

The ENST00000649263.1(ENSG00000285713):​n.328-93167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,902 control chromosomes in the GnomAD database, including 54,154 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 0.84 (54153 hom., cov: 29)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ENSG00000285713 ENST00000649263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 4 publications found

Genes affected

ENSG00000285713 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649263.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285713	ENST00000649263.1		n.328-93167A>G		intron	N/A	ENSP00000497507.1	A0A3B3ISY7
	ENSG00000285783	ENST00000648340.1		n.138+96A>G		intron	N/A
	ENSG00000285783	ENST00000650526.1		n.223-93167A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127653 AN: 151778 Hom.: 54082 Cov.: 29

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.821

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 AF XY: 0.00 AC XY: 0 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) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

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: 0.841 AC: 127784 AN: 151896 Hom.: 54153 Cov.: 29 AF XY: 0.842 AC XY: 62481 AN XY: 74218

African (AFR) AF: 0.950 AC: 39381 AN: 41458

American (AMR) AF: 0.811 AC: 12377 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2554 AN: 3462

East Asian (EAS) AF: 0.860 AC: 4399 AN: 5114

South Asian (SAS) AF: 0.780 AC: 3731 AN: 4786

European-Finnish (FIN) AF: 0.840 AC: 8860 AN: 10550

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53801 AN: 67948

Other (OTH) AF: 0.818 AC: 1727 AN: 2110

Alfa AF: 0.798 Hom.: 80541

Bravo AF: 0.844

Asia WGS AF: 0.793 AC: 2757 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.25
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs6827794; hg19: chr4-145430297;