4-148725386-T-C

Variant names:

• chr4-148725386-T-C
• rs28435578
• ENST00000661928.1:n.223-141371T>C

Variant summary

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

The ENST00000661928.1(ENSG00000287292):​n.223-141371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,102 control chromosomes in the GnomAD database, including 4,850 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 0.23 (4850 hom., cov: 32)
• Consequence: ENSG00000287292 ENST00000661928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 8 publications found

Genes affected

ENSG00000287292 (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 (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986195	XR_001741441.2	n.3662-141371T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287292	ENST00000661928.1	n.223-141371T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35360 AN: 151984 Hom.: 4849 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.233 AC: 35382 AN: 152102 Hom.: 4850 Cov.: 32 AF XY: 0.226 AC XY: 16777 AN XY: 74396

African (AFR) AF: 0.384 AC: 15903 AN: 41450

American (AMR) AF: 0.166 AC: 2539 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3470

East Asian (EAS) AF: 0.0633 AC: 328 AN: 5184

South Asian (SAS) AF: 0.149 AC: 719 AN: 4828

European-Finnish (FIN) AF: 0.115 AC: 1223 AN: 10592

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13321 AN: 67980

Other (OTH) AF: 0.230 AC: 485 AN: 2112

Alfa AF: 0.148 Hom.: 377

Bravo AF: 0.246

Asia WGS AF: 0.113 AC: 396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		0.099

Splicing

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

Other links and lift over

dbSNP: rs28435578; hg19: chr4-149646538;