6-3851311-G-C

Position:

• chr6-3851311-G-C

Variant summary

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

The NM_012135.3(FAM50B):​c.*522G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 171,118 control chromosomes in the GnomAD database, including 17,545 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 0.43 (14500 hom., cov: 33)
  • Exomes 𝑓: 0.55 (3045 hom.)
• Consequence: FAM50B NM_012135.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

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]

ENSG00000238158 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM50B	NM_012135.3	c.*522G>C		3_prime_UTR_variant	2/2	ENST00000648326.1	NP_036267.1
FAM50B	XM_017010729.2	c.*522G>C		3_prime_UTR_variant	2/2		XP_016866218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM50B	ENST00000648326.1	c.*522G>C		3_prime_UTR_variant	2/2		NM_012135.3	ENSP00000496837.1
FAM50B	ENST00000380274.2	c.*522G>C		3_prime_UTR_variant	1/1	6		ENSP00000369627.1
ENSG00000238158	ENST00000454396.2	n.80-4159G>C		intron_variant		5
ENSG00000233068	ENST00000648025.1	n.76+19300G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64881 AN: 151932 Hom.: 14490 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.553 AC: 10550 AN: 19068 Hom.: 3045 Cov.: 0 AF XY: 0.548 AC XY: 5026 AN XY: 9174

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.427 AC: 64936 AN: 152050 Hom.: 14500 Cov.: 33 AF XY: 0.429 AC XY: 31867 AN XY: 74320

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.394

Alfa AF: 0.353 Hom.: 1165

Bravo AF: 0.406

Asia WGS AF: 0.246 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3196512; hg19: chr6-3851545; COSMIC: COSV66655401;