rs2296129

Positions:

• chr20-56536308-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013646.4(FAM209B):​c.386A>C​(p.Glu129Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,613,934 control chromosomes in the GnomAD database, including 5,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.023 (563 hom., cov: 32)
  • Exomes 𝑓: 0.018 (4549 hom.)
• Consequence: FAM209B NM_001013646.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

FAM209B (HGNC:16101): (family with sequence similarity 209 member B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3432245E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM209B	NM_001013646.4	c.386A>C	p.Glu129Ala	missense_variant	2/2	ENST00000371325.1	NP_001013668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM209B	ENST00000371325.1	c.386A>C	p.Glu129Ala	missense_variant	2/2	1	NM_001013646.4	ENSP00000360376.1

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3438 AN: 152136 Hom.: 560 Cov.: 32

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0467 AC: 11730 AN: 251200 Hom.: 2171 AF XY: 0.0426 AC XY: 5782 AN XY: 135780

Gnomad AFR exome AF: 0.00750

Gnomad AMR exome AF: 0.0502

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.475

Gnomad SAS exome AF: 0.0262

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.0256

GnomAD4 exome AF: 0.0176 AC: 25768 AN: 1461680 Hom.: 4549 Cov.: 31 AF XY: 0.0174 AC XY: 12623 AN XY: 727132

Gnomad4 AFR exome AF: 0.00693

Gnomad4 AMR exome AF: 0.0480

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.0256

Gnomad4 FIN exome AF: 0.000973

Gnomad4 NFE exome AF: 0.000828

Gnomad4 OTH exome AF: 0.0280

GnomAD4 genome AF: 0.0226 AC: 3446 AN: 152254 Hom.: 563 Cov.: 32 AF XY: 0.0257 AC XY: 1913 AN XY: 74452

Gnomad4 AFR AF: 0.00820

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0188 Hom.: 910

Bravo AF: 0.0274

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00840 AC: 37

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.0443 AC: 5383

Asia WGS AF: 0.182 AC: 629 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.00033	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.076
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		0.0010	B
Vest4		0.060
MPC		0.51
ClinPred		0.016	T
GERP RS		1.2
Varity_R		0.085
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2296129; hg19: chr20-55111364;