ENST00000454396.2:n.79+4953G>A

Variant names:

• chr6-3836964-G-A
• rs17318866
• ENST00000454396.2:n.79+4953G>A

Variant summary

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

The ENST00000454396.2(ENSG00000233068):​n.79+4953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,012 control chromosomes in the GnomAD database, including 6,050 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 0.27 (6050 hom., cov: 32)
• Consequence: ENSG00000233068 ENST00000454396.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 5 publications found

Genes affected

ENSG00000233068 (HGNC:):

FAM50B (HGNC:18789): (family with sequence similarity 50 member B) This gene contains an intronless ORF that arose from ancestral retroposition. The encoded protein is related to a plant protein that plays a role in the circadian clock. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in many tissues. [provided by RefSeq, Nov 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	XM_017010729.2	c.-24+4953G>A		intron_variant	Intron 1 of 1		XP_016866218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000233068	ENST00000454396.2	n.79+4953G>A		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.2	n.132+4953G>A		intron_variant	Intron 1 of 4
ENSG00000233068	ENST00000780356.1	n.92+4953G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40585 AN: 151894 Hom.: 6053 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.267 AC: 40583 AN: 152012 Hom.: 6050 Cov.: 32 AF XY: 0.265 AC XY: 19714 AN XY: 74286

African (AFR) AF: 0.133 AC: 5537 AN: 41482

American (AMR) AF: 0.314 AC: 4801 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1162 AN: 5162

South Asian (SAS) AF: 0.247 AC: 1188 AN: 4812

European-Finnish (FIN) AF: 0.283 AC: 2977 AN: 10538

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22685 AN: 67960

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.309 Hom.: 10160

Bravo AF: 0.264

Asia WGS AF: 0.250 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.48
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs17318866; hg19: chr6-3837198;