rs11001296

Variant names:

• chr10-75113669-T-C
• rs11001296
• NM_001174156.2:c.-16+1947T>C

Variant summary

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

The NM_001174156.2(SAMD8):​c.-16+1947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,168 control chromosomes in the GnomAD database, including 5,714 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 0.26 (5714 hom., cov: 33)
• Consequence: SAMD8 NM_001174156.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 6 publications found

Genes affected

SAMD8 (HGNC:26320): (sterile alpha motif domain containing 8) Predicted to enable ceramide cholinephosphotransferase activity and sphingomyelin synthase activity. Involved in ceramide biosynthetic process and regulation of ceramide biosynthetic process. Located in cytosol and endoplasmic reticulum. Is integral component of endoplasmic reticulum membrane. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD8	NM_001174156.2	c.-16+1947T>C		intron_variant	Intron 1 of 5	ENST00000542569.6	NP_001167627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD8	ENST00000542569.6	c.-16+1947T>C		intron_variant	Intron 1 of 5	1	NM_001174156.2	ENSP00000438042.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39875 AN: 152050 Hom.: 5715 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.262 AC: 39892 AN: 152168 Hom.: 5714 Cov.: 33 AF XY: 0.260 AC XY: 19334 AN XY: 74402

African (AFR) AF: 0.371 AC: 15408 AN: 41508

American (AMR) AF: 0.281 AC: 4292 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1645 AN: 5184

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1570 AN: 10592

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13883 AN: 67992

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.230 Hom.: 5095

Bravo AF: 0.281

Asia WGS AF: 0.310 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.52
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: rs11001296; hg19: chr10-76873427;