1-27935898-A-T

Variant summary

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

The NM_014474.4(SMPDL3B):c.61+654A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,764 control chromosomes in the GnomAD database, including 29,239 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 0.61 (29239 hom., cov: 30)
• Consequence: SMPDL3B NM_014474.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

SMPDL3B (HGNC:21416): (sphingomyelin phosphodiesterase acid like 3B) Enables phosphoric diester hydrolase activity. Predicted to be involved in membrane lipid catabolic process; negative regulation of inflammatory response; and negative regulation of toll-like receptor signaling pathway. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMPDL3B	NM_014474.4	c.61+654A>T		intron_variant		ENST00000373894.8
SMPDL3B	NM_001009568.3	c.61+654A>T		intron_variant
SMPDL3B	NM_001304579.2	c.-629+654A>T		intron_variant
SMPDL3B	XM_011541259.3	c.61+654A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMPDL3B	ENST00000373894.8	c.61+654A>T		intron_variant		1	NM_014474.4	P1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 91979 AN: 151646 Hom.: 29222 Cov.: 30

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.606 AC: 92025 AN: 151764 Hom.: 29239 Cov.: 30 AF XY: 0.608 AC XY: 45078 AN XY: 74164

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.613

Alfa AF: 0.644 Hom.: 3868

Bravo AF: 0.590

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.059
Dann	Benign	0.82

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: rs4409675; hg19: chr1-28262409; COSMIC: COSV65870283; COSMIC: COSV65870283;