rs285757

Variant names:

• chr15-92635945-T-C
• rs285757
• NM_207446.3:c.345-5600A>G

Variant summary

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

The NM_207446.3(FAM174B):​c.345-5600A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,042 control chromosomes in the GnomAD database, including 2,219 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 0.17 (2219 hom., cov: 31)
• Consequence: FAM174B NM_207446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.89
• Publications: 13 publications found

Genes affected

FAM174B (HGNC:34339): (family with sequence similarity 174 member B) Involved in Golgi organization. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207446.3. 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
	FAM174B	NM_207446.3	MANE Select	c.345-5600A>G		intron	N/A	NP_997329.2	Q3ZCQ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM174B	ENST00000327355.6	TSL:1 MANE Select	c.345-5600A>G		intron	N/A	ENSP00000329040.5	Q3ZCQ3
	FAM174B	ENST00000896008.1		c.345-16486A>G		intron	N/A	ENSP00000566067.1
	FAM174B	ENST00000555064.5	TSL:4	c.-81+3213A>G		intron	N/A	ENSP00000455765.1	G3V5D1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25220 AN: 151924 Hom.: 2221 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.166 AC: 25216 AN: 152042 Hom.: 2219 Cov.: 31 AF XY: 0.163 AC XY: 12078 AN XY: 74322

African (AFR) AF: 0.149 AC: 6189 AN: 41452

American (AMR) AF: 0.138 AC: 2109 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3468

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5174

South Asian (SAS) AF: 0.129 AC: 624 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10552

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13432 AN: 67978

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.184 Hom.: 8782

Bravo AF: 0.164

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.15
DANN	Benign	0.46
PhyloP100		-3.9
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: rs285757; hg19: chr15-93179175;