chr8-118495176-G-C

Variant names:

• chr8-118495176-G-C
• rs4514016
• NM_207506.3:c.193-55215C>G

Variant summary

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

The NM_207506.3(SAMD12):​c.193-55215C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,164 control chromosomes in the GnomAD database, including 1,257 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 0.12 (1257 hom., cov: 32)
• Consequence: SAMD12 NM_207506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD12	NM_207506.3	c.193-55215C>G		intron_variant	Intron 2 of 3	ENST00000314727.9	NP_997389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD12	ENST00000314727.9	c.193-55215C>G		intron_variant	Intron 2 of 3	1	NM_207506.3	ENSP00000314173.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18666 AN: 152046 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.123 AC: 18715 AN: 152164 Hom.: 1257 Cov.: 32 AF XY: 0.128 AC XY: 9542 AN XY: 74406

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0593 Hom.: 70

Bravo AF: 0.115

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs4514016; hg19: chr8-119507415;