NM_001136570.3:c.561-433A>G

Variant names:

• chr4-76268227-A-G
• rs10025494
• NM_001136570.3:c.561-433A>G

Variant summary

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

The NM_001136570.3(FAM47E):​c.561-433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 164,492 control chromosomes in the GnomAD database, including 4,338 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 0.22 (4089 hom., cov: 32)
  • Exomes 𝑓: 0.18 (249 hom.)
• Consequence: FAM47E NM_001136570.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136570.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47E	NM_001136570.3	MANE Select	c.561-433A>G		intron	N/A	NP_001130042.1
	FAM47E-STBD1	NM_001242939.2		c.561-433A>G		intron	N/A	NP_001229868.1
	FAM47E	NM_001242936.1		c.222-433A>G		intron	N/A	NP_001229865.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47E	ENST00000424749.7	TSL:5 MANE Select	c.561-433A>G		intron	N/A	ENSP00000409423.2
	FAM47E-STBD1	ENST00000515604.5	TSL:2	c.561-433A>G		intron	N/A	ENSP00000422067.1
	FAM47E	ENST00000853410.1		c.561-433A>G		intron	N/A	ENSP00000523469.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33984 AN: 151908 Hom.: 4081 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.183 AC: 2287 AN: 12466 Hom.: 249 Cov.: 0 AF XY: 0.186 AC XY: 1186 AN XY: 6390

African (AFR) AF: 0.235 AC: 16 AN: 68

American (AMR) AF: 0.170 AC: 45 AN: 264

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 23 AN: 242

East Asian (EAS) AF: 0.0154 AC: 2 AN: 130

South Asian (SAS) AF: 0.200 AC: 237 AN: 1184

European-Finnish (FIN) AF: 0.189 AC: 181 AN: 960

Middle Eastern (MID) AF: 0.219 AC: 7 AN: 32

European-Non Finnish (NFE) AF: 0.185 AC: 1625 AN: 8786

Other (OTH) AF: 0.189 AC: 151 AN: 800

GnomAD4 genome AF: 0.224 AC: 34037 AN: 152026 Hom.: 4089 Cov.: 32 AF XY: 0.225 AC XY: 16704 AN XY: 74324

African (AFR) AF: 0.290 AC: 12034 AN: 41432

American (AMR) AF: 0.186 AC: 2845 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3470

East Asian (EAS) AF: 0.0294 AC: 152 AN: 5174

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4810

European-Finnish (FIN) AF: 0.231 AC: 2447 AN: 10572

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14392 AN: 67976

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.207 Hom.: 1854

Bravo AF: 0.221

Asia WGS AF: 0.144 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.37
PhyloP100		-0.91
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: rs10025494; hg19: chr4-77189380;