chr8-118154455-T-C

Variant names:

• chr8-118154455-T-C
• rs723268
• NR_146234.2:n.611-9072A>G

Variant summary

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

The NR_146234.2(SAMD12):​n.611-9072A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,128 control chromosomes in the GnomAD database, including 42,135 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 0.73 (42135 hom., cov: 32)
• Consequence: SAMD12 NR_146234.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 1 publications found

Genes affected

SAMD12 (HGNC:31750): (sterile alpha motif domain containing 12) Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasmic side of plasma membrane. Implicated in familial adult myoclonic epilepsy 1. [provided by Alliance of Genome Resources, Apr 2022]

SAMD12 Gene-Disease associations (from GenCC):

• epilepsy, familial adult myoclonic, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD12	NR_146234.2	n.611-9072A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111037 AN: 152010 Hom.: 42129 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.730 AC: 111084 AN: 152128 Hom.: 42135 Cov.: 32 AF XY: 0.729 AC XY: 54245 AN XY: 74366

African (AFR) AF: 0.520 AC: 21554 AN: 41468

American (AMR) AF: 0.711 AC: 10857 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2874 AN: 3470

East Asian (EAS) AF: 0.732 AC: 3786 AN: 5172

South Asian (SAS) AF: 0.638 AC: 3077 AN: 4820

European-Finnish (FIN) AF: 0.884 AC: 9373 AN: 10600

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56957 AN: 68018

Other (OTH) AF: 0.735 AC: 1547 AN: 2106

Alfa AF: 0.777 Hom.: 5805

Bravo AF: 0.712

Asia WGS AF: 0.651 AC: 2265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.26
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs723268; hg19: chr8-119166694;