rs6030315

Variant names:

• chr20-36941421-C-A
• rs6030315
• NM_015474.4:c.276-310G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

SAMHD1 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 5

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• Moyamoya disease

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• Aicardi-Goutieres syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial chilblain lupus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• chilblain lupus 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• chilblain lupus

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

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 (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015474.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMHD1	NM_015474.4	MANE Select	c.276-310G>T		intron	N/A	NP_056289.2
	SAMHD1	NM_001363729.2		c.276-310G>T		intron	N/A	NP_001350658.1
	SAMHD1	NM_001363733.2		c.276-310G>T		intron	N/A	NP_001350662.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMHD1	ENST00000646673.2	MANE Select	c.276-310G>T		intron	N/A	ENSP00000493536.2
	SAMHD1	ENST00000262878.5	TSL:1	c.276-310G>T		intron	N/A	ENSP00000262878.5
	SAMHD1	ENST00000866371.1		c.276-310G>T		intron	N/A	ENSP00000536430.1

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

African (AFR) AF: 0.756 AC: 31346 AN: 41444

American (AMR) AF: 0.545 AC: 8315 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2536 AN: 5176

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4812

European-Finnish (FIN) AF: 0.508 AC: 5354 AN: 10546

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27014 AN: 67936

Other (OTH) AF: 0.507 AC: 1070 AN: 2110

Alfa AF: 0.431 Hom.: 8534

Bravo AF: 0.539

Asia WGS AF: 0.451 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-1.1
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: rs6030315; hg19: chr20-35569824;