rs4689973

Variant names:

• chr4-5013282-C-T
• rs4689973
• ENST00000774609.1:n.356+8649C>T

Variant summary

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

The ENST00000774609.1(ENSG00000300857):​n.356+8649C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,074 control chromosomes in the GnomAD database, including 2,167 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 0.15 (2167 hom., cov: 33)
• Consequence: ENSG00000300857 ENST00000774609.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 2 publications found

Genes affected

ENSG00000300857 (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 (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000774609.1. 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
	ENSG00000300857	ENST00000774609.1		n.356+8649C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22535 AN: 151956 Hom.: 2162 Cov.: 33

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.148 AC: 22550 AN: 152074 Hom.: 2167 Cov.: 33 AF XY: 0.153 AC XY: 11344 AN XY: 74320

African (AFR) AF: 0.0347 AC: 1442 AN: 41506

American (AMR) AF: 0.264 AC: 4027 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.129 AC: 665 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1309 AN: 4808

European-Finnish (FIN) AF: 0.168 AC: 1767 AN: 10548

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12138 AN: 67984

Other (OTH) AF: 0.167 AC: 353 AN: 2108

Alfa AF: 0.168 Hom.: 487

Bravo AF: 0.148

Asia WGS AF: 0.182 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.48
PhyloP100		-0.53

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4689973;

hg19: chr4-5015009;

COSMIC: COSV57036717;