NM_058186.4:c.163+3914A>G

Variant names:

• chr21-41326980-A-G
• rs441810
• NM_058186.4:c.163+3914A>G

Variant summary

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

The NM_058186.4(FAM3B):​c.163+3914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,120 control chromosomes in the GnomAD database, including 13,127 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 0.35 (13127 hom., cov: 33)
• Consequence: FAM3B NM_058186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 23 publications found

Genes affected

FAM3B (HGNC:1253): (FAM3 metabolism regulating signaling molecule B) Involved in insulin secretion. Located in extracellular exosome. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058186.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3B	NM_058186.4	MANE Select	c.163+3914A>G		intron	N/A	NP_478066.3
	FAM3B	NM_206964.2		c.19+10082A>G		intron	N/A	NP_996847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3B	ENST00000357985.7	TSL:1 MANE Select	c.163+3914A>G		intron	N/A	ENSP00000350673.2
	FAM3B	ENST00000398652.7	TSL:1	c.280+3914A>G		intron	N/A	ENSP00000381646.3
	FAM3B	ENST00000398647.7	TSL:1	c.19+10082A>G		intron	N/A	ENSP00000381642.3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53707 AN: 152002 Hom.: 13069 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.354 AC: 53827 AN: 152120 Hom.: 13127 Cov.: 33 AF XY: 0.345 AC XY: 25648 AN XY: 74372

African (AFR) AF: 0.697 AC: 28941 AN: 41496

American (AMR) AF: 0.290 AC: 4430 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1053 AN: 5162

South Asian (SAS) AF: 0.151 AC: 727 AN: 4816

European-Finnish (FIN) AF: 0.119 AC: 1262 AN: 10614

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.226 AC: 15361 AN: 67986

Other (OTH) AF: 0.345 AC: 727 AN: 2108

Alfa AF: 0.264 Hom.: 27580

Bravo AF: 0.380

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.35
PhyloP100		-1.1
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: rs441810; hg19: chr21-42698907;