rs2277324

Positions:

• chr12-57619392-G-A

Variant summary

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

The ENST00000474359.7(ENSG00000287908):​n.*144G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 327,142 control chromosomes in the GnomAD database, including 20,275 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 0.32 (8836 hom., cov: 32)
  • Exomes 𝑓: 0.35 (11439 hom.)
• Consequence: ENSG00000287908 ENST00000474359.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

ENSG00000287908 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927583	NR_120450.1	n.2120+239C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000287908	ENST00000474359.7	n.*144G>A		non_coding_transcript_exon_variant	7/23	5		ENSP00000431994.2
ENSG00000287908	ENST00000474359.7	n.*144G>A		3_prime_UTR_variant	7/23	5		ENSP00000431994.2
ENSG00000224713	ENST00000593846.1	n.73+174C>T		intron_variant		5
ENSG00000287908	ENST00000477314.1	n.*13G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48743 AN: 152004 Hom.: 8841 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.346 AC: 60533 AN: 175020 Hom.: 11439 Cov.: 0 AF XY: 0.334 AC XY: 31813 AN XY: 95300

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.320 AC: 48738 AN: 152122 Hom.: 8836 Cov.: 32 AF XY: 0.316 AC XY: 23504 AN XY: 74370

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.399

Alfa AF: 0.410 Hom.: 16537

Bravo AF: 0.316

Asia WGS AF: 0.242 AC: 843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.96
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277324; hg19: chr12-58013175; COSMIC: COSV54085899;