rs4140388

Positions:

• chr4-99144583-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000500358.6(ENSG00000246090):​n.680-9962G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,048 control chromosomes in the GnomAD database, including 24,395 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 0.56 (24395 hom., cov: 33)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

Genes affected

ENSG00000246090 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507053	NR_037884.1	n.680-9962G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000246090	ENST00000500358.6	n.680-9962G>C		intron_variant		1
ADH4	ENST00000504581.1	n.170-1803C>G		intron_variant		3
ENSG00000246090	ENST00000661393.1	n.676+10778G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85098 AN: 151930 Hom.: 24368 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.560 AC: 85178 AN: 152048 Hom.: 24395 Cov.: 33 AF XY: 0.564 AC XY: 41904 AN XY: 74308

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.546

Alfa AF: 0.545 Hom.: 2831

Bravo AF: 0.564

Asia WGS AF: 0.522 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4140388; hg19: chr4-100065734;