rs115645414

Variant names:

• chr20-36892887-G-A
• rs115645414
• NM_015474.4:c.*45C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-36892887-G-A
• chr20-36892887-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015474.4(SAMHD1):​c.*45C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000849 in 1,611,640 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (4 hom.)
• Consequence: SAMHD1 NM_015474.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.232
• Publications: 0 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]

TLDC2 (HGNC:16112): (TBC/LysM-associated domain containing 2) Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within negative regulation of oxidative stress-induced neuron death. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-36892887-G-A is Benign according to our data. Variant chr20-36892887-G-A is described in ClinVar as Benign. ClinVar VariationId is 338339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0038 (578/152164) while in subpopulation AFR AF = 0.0123 (510/41508). AF 95% confidence interval is 0.0114. There are 3 homozygotes in GnomAd4. There are 282 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

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.*45C>T		3_prime_UTR	Exon 16 of 16	NP_056289.2
	TLDC2	NM_080628.3	MANE Select	c.*43G>A		3_prime_UTR	Exon 7 of 7	NP_542195.1	A0PJX2
	SAMHD1	NM_001363729.2		c.*45C>T		3_prime_UTR	Exon 15 of 15	NP_001350658.1	Q9Y3Z3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMHD1	ENST00000646673.2	MANE Select	c.*45C>T		3_prime_UTR	Exon 16 of 16	ENSP00000493536.2	Q9Y3Z3-1
	TLDC2	ENST00000217320.8	TSL:1 MANE Select	c.*43G>A		3_prime_UTR	Exon 7 of 7	ENSP00000217320.3	A0PJX2
	SAMHD1	ENST00000262878.5	TSL:1	c.*45C>T		3_prime_UTR	Exon 15 of 15	ENSP00000262878.5	Q9Y3Z3-4

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 569 AN: 152046 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00112 AC: 278 AN: 249052 AF XY: 0.000942

Gnomad AFR exome AF: 0.0114

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000242

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000541 AC: 790 AN: 1459476 Hom.: 4 Cov.: 29 AF XY: 0.000503 AC XY: 365 AN XY: 726264

African (AFR) AF: 0.0130 AC: 433 AN: 33422

American (AMR) AF: 0.00172 AC: 77 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5766

European-Non Finnish (NFE) AF: 0.000163 AC: 181 AN: 1109874

Other (OTH) AF: 0.00134 AC: 81 AN: 60292

GnomAD4 genome AF: 0.00380 AC: 578 AN: 152164 Hom.: 3 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74364

African (AFR) AF: 0.0123 AC: 510 AN: 41508

American (AMR) AF: 0.00334 AC: 51 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00162 Hom.: 1

Bravo AF: 0.00413

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Aicardi-Goutieres syndrome 5 (1)
-	-	1	Chilblain lupus 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.80
DANN	Benign	0.25
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs115645414; hg19: chr20-35521290; COSMIC: COSV107254272; COSMIC: COSV107254272;