20-36896959-A-G

Variant summary

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

The NM_015474.4(SAMHD1):c.1746+863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,834 control chromosomes in the GnomAD database, including 24,598 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 0.54 (24598 hom., cov: 31)
• Consequence: SAMHD1 NM_015474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

SAMHD1 (HGNC:15925): (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1) This gene may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. Mutations in this gene have been associated with Aicardi-Goutieres syndrome. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMHD1	NM_015474.4	c.1746+863T>C		intron_variant		ENST00000646673.2
SAMHD1	NM_001363729.2	c.1641+863T>C		intron_variant
SAMHD1	NM_001363733.2	c.1746+863T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMHD1	ENST00000646673.2	c.1746+863T>C		intron_variant			NM_015474.4	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82721 AN: 151716 Hom.: 24587 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.545 AC: 82740 AN: 151834 Hom.: 24598 Cov.: 31 AF XY: 0.546 AC XY: 40514 AN XY: 74180

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.563

Alfa AF: 0.638 Hom.: 15403

Bravo AF: 0.523

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.2
Dann	Benign	0.80

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: rs1291142; hg19: chr20-35525362;