12-13061603-A-G

Variant names:

• chr12-13061603-A-G
• rs3741818
• NM_020853.2:c.561A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_020853.2(FAM234B):​c.561A>G​(p.Val187Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,612,674 control chromosomes in the GnomAD database, including 542,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.73 (41896 hom., cov: 31)
  • Exomes 𝑓: 0.82 (500694 hom.)
• Consequence: FAM234B NM_020853.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.859

Genes affected

FAM234B (HGNC:29288): (family with sequence similarity 234 member B) Predicted to be located in Golgi apparatus and cytoskeleton. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-13061603-A-G is Benign according to our data. Variant chr12-13061603-A-G is described in ClinVar as [Benign]. Clinvar id is 3060677.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.859 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM234B	NM_020853.2	c.561A>G	p.Val187Val	synonymous_variant	Exon 4 of 13	ENST00000197268.13	NP_065904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM234B	ENST00000197268.13	c.561A>G	p.Val187Val	synonymous_variant	Exon 4 of 13	1	NM_020853.2	ENSP00000197268.8
FAM234B	ENST00000416494.6	n.561A>G		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000394063.2
FAM234B	ENST00000537625.1	c.-112A>G		upstream_gene_variant		1		ENSP00000437974.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110412 AN: 151636 Hom.: 41897 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.748

GnomAD3 exomes AF: 0.745 AC: 186428 AN: 250076 Hom.: 71801 AF XY: 0.757 AC XY: 102280 AN XY: 135084

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.767

Gnomad EAS exome AF: 0.470

Gnomad SAS exome AF: 0.726

Gnomad FIN exome AF: 0.787

Gnomad NFE exome AF: 0.856

Gnomad OTH exome AF: 0.784

GnomAD4 exome AF: 0.823 AC: 1201736 AN: 1460920 Hom.: 500694 Cov.: 43 AF XY: 0.821 AC XY: 596812 AN XY: 726698

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.637

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.791

Gnomad4 NFE exome AF: 0.862

Gnomad4 OTH exome AF: 0.797

GnomAD4 genome AF: 0.728 AC: 110429 AN: 151754 Hom.: 41896 Cov.: 31 AF XY: 0.723 AC XY: 53620 AN XY: 74144

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.748

Alfa AF: 0.817 Hom.: 64205

Bravo AF: 0.709

Asia WGS AF: 0.569 AC: 1982 AN: 3478

EpiCase AF: 0.854

EpiControl AF: 0.852

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FAM234B-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.4
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3741818; hg19: chr12-13214537; COSMIC: COSV52195016; COSMIC: COSV52195016;