2-131521067-G-C

Variant names:

• chr2-131521067-G-C
• rs705090
• ENST00000438378.3:n.3279G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000438378.3(SMPD4BP):​n.3279G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 148,622 control chromosomes in the GnomAD database, including 13,695 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 0.40 (13695 hom., cov: 27)
  • Exomes 𝑓: 0.23 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMPD4BP ENST00000438378.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 2 publications found

Genes affected

SMPD4BP (HGNC:):

SMPD4BP (HGNC:24761): (sphingomyelin phosphodiesterase 4B, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMPD4BP	NR_026922.1	n.3279G>C		non_coding_transcript_exon_variant	Exon 18 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMPD4BP	ENST00000438378.3	n.3279G>C		non_coding_transcript_exon_variant	Exon 18 of 18	1
SMPD4BP	ENST00000850260.1	n.3046G>C		non_coding_transcript_exon_variant	Exon 20 of 20

Frequencies

GnomAD3 genomes AF: 0.404 AC: 59989 AN: 148512 Hom.: 13660 Cov.: 27

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.421

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.228 AC: 106 AN: 464 Hom.: 15 Cov.: 0 AF XY: 0.244 AC XY: 64 AN XY: 262

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.277 AC: 87 AN: 314

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.134 AC: 19 AN: 142

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.404 AC: 60086 AN: 148622 Hom.: 13695 Cov.: 27 AF XY: 0.411 AC XY: 29777 AN XY: 72416

African (AFR) AF: 0.568 AC: 22655 AN: 39918

American (AMR) AF: 0.494 AC: 7332 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1449 AN: 3424

East Asian (EAS) AF: 0.671 AC: 3353 AN: 5000

South Asian (SAS) AF: 0.368 AC: 1710 AN: 4650

European-Finnish (FIN) AF: 0.316 AC: 3253 AN: 10292

Middle Eastern (MID) AF: 0.355 AC: 100 AN: 282

European-Non Finnish (NFE) AF: 0.283 AC: 19039 AN: 67252

Other (OTH) AF: 0.427 AC: 877 AN: 2054

Alfa AF: 0.163 Hom.: 276

Bravo AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.35
PhyloP100		-0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs705090; hg19: chr2-132278640; COSMIC: COSV70286011;