chr4-76277833-C-T

Variant names:

• chr4-76277833-C-T
• rs6812193
• NM_001136570.3:c.871-236C>T

Variant summary

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

The NM_001136570.3(FAM47E):​c.871-236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,046 control chromosomes in the GnomAD database, including 11,039 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 0.37 (11039 hom., cov: 32)
• Consequence: FAM47E NM_001136570.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 100 publications found

Genes affected

FAM47E (HGNC:34343): (family with sequence similarity 47 member E) Enables enzyme activator activity. Involved in positive regulation of histone methylation and protein localization to chromatin. Located in chromatin; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM47E-STBD1 (HGNC:44667): (FAM47E-STBD1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FAM47E (family with sequence similarity 47, member E) and STBD1 (starch binding domain 1) genes on chromosome 4. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Jul 2011]

ENSG00000287401 (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 = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3	c.871-236C>T		intron_variant	Intron 5 of 7	ENST00000424749.7	NP_001130042.1
FAM47E-STBD1	NM_001242939.2	c.871-236C>T		intron_variant	Intron 5 of 6		NP_001229868.1
FAM47E	NM_001242936.1	c.577-236C>T		intron_variant	Intron 5 of 7		NP_001229865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47E	ENST00000424749.7	c.871-236C>T		intron_variant	Intron 5 of 7	5	NM_001136570.3	ENSP00000409423.2
FAM47E-STBD1	ENST00000515604.5	c.871-236C>T		intron_variant	Intron 5 of 6	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56711 AN: 151926 Hom.: 11034 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.373 AC: 56762 AN: 152046 Hom.: 11039 Cov.: 32 AF XY: 0.370 AC XY: 27475 AN XY: 74326

African (AFR) AF: 0.446 AC: 18514 AN: 41476

American (AMR) AF: 0.304 AC: 4646 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3468

East Asian (EAS) AF: 0.0823 AC: 426 AN: 5178

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4820

European-Finnish (FIN) AF: 0.359 AC: 3793 AN: 10552

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25715 AN: 67952

Other (OTH) AF: 0.370 AC: 778 AN: 2104

Alfa AF: 0.364 Hom.: 46504

Bravo AF: 0.368

Asia WGS AF: 0.209 AC: 729 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	6.5
DANN	Benign	0.61
PhyloP100		0.070
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6812193; hg19: chr4-77198986;