rs6517664

Variant names:

• chr21-41333056-C-T
• rs6517664
• NM_058186.4:c.164-5322C>T

Variant summary

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

The NM_058186.4(FAM3B):​c.164-5322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 147,896 control chromosomes in the GnomAD database, including 725 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 0.083 (725 hom., cov: 31)
• Consequence: FAM3B NM_058186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3B	NM_058186.4	c.164-5322C>T		intron_variant	Intron 2 of 7	ENST00000357985.7	NP_478066.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3B	ENST00000357985.7	c.164-5322C>T		intron_variant	Intron 2 of 7	1	NM_058186.4	ENSP00000350673.2
FAM3B	ENST00000398652.7	c.281-5322C>T		intron_variant	Intron 3 of 8	1		ENSP00000381646.3

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12204 AN: 147834 Hom.: 722 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0789

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0749

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

GnomAD4 genome AF: 0.0827 AC: 12228 AN: 147896 Hom.: 725 Cov.: 31 AF XY: 0.0809 AC XY: 5815 AN XY: 71884

African (AFR) AF: 0.166 AC: 6689 AN: 40296

American (AMR) AF: 0.0608 AC: 906 AN: 14898

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 178 AN: 3428

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5064

South Asian (SAS) AF: 0.0202 AC: 95 AN: 4706

European-Finnish (FIN) AF: 0.0335 AC: 299 AN: 8920

Middle Eastern (MID) AF: 0.0714 AC: 20 AN: 280

European-Non Finnish (NFE) AF: 0.0564 AC: 3797 AN: 67338

Other (OTH) AF: 0.0744 AC: 153 AN: 2056

Alfa AF: 0.0646 Hom.: 517

Bravo AF: 0.0871

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.84
PhyloP100		-1.9
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: rs6517664; hg19: chr21-42704983;