rs6030315

chr20-36941421-C-A

Variant summary

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

The NM_015474.4(SAMHD1):c.276-310G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,938 control chromosomes in the GnomAD database, including 22,597 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 0.52 (22597 hom., cov: 32)
• Consequence: SAMHD1 NM_015474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMHD1	NM_015474.4	c.276-310G>T		intron_variant		ENST00000646673.2
SAMHD1	NM_001363729.2	c.276-310G>T		intron_variant
SAMHD1	NM_001363733.2	c.276-310G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMHD1	ENST00000646673.2	c.276-310G>T		intron_variant			NM_015474.4	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79078 AN: 151820 Hom.: 22545 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.521 AC: 79180 AN: 151938 Hom.: 22597 Cov.: 32 AF XY: 0.521 AC XY: 38685 AN XY: 74238

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.507

Alfa AF: 0.430 Hom.: 7642

Bravo AF: 0.539

Asia WGS AF: 0.451 AC: 1569 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	1.5
Dann	Benign	0.66

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: rs6030315; hg19: chr20-35569824;