rs2246154

chr20-1547392-A-Cchr20-1547392-A-G

Variant summary

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

The NM_178460.3(SIRPD):c.421+4299T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,220 control chromosomes in the GnomAD database, including 56,386 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 0.86 (56386 hom., cov: 32)
• Consequence: SIRPD NM_178460.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949

Genes affected

SIRPD (HGNC:16248): (signal regulatory protein delta) Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRPD	NM_178460.3	c.421+4299T>G		intron_variant		ENST00000381623.4
LOC105372499	XR_001754464.2	n.651-2656A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRPD	ENST00000381623.4	c.421+4299T>G		intron_variant		1	NM_178460.3	A2
	ENST00000453770.1	n.802+4299T>G		intron_variant, non_coding_transcript_variant
SIRPD	ENST00000381621.5	c.421+4299T>G		intron_variant		3		P2
SIRPD	ENST00000429387.5	c.69+4479T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130620 AN: 152102 Hom.: 56338 Cov.: 32

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.859 AC: 130718 AN: 152220 Hom.: 56386 Cov.: 32 AF XY: 0.856 AC XY: 63700 AN XY: 74416

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.862

Alfa AF: 0.831 Hom.: 3035

Bravo AF: 0.851

Asia WGS AF: 0.835 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.66
Dann	Benign	0.54

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: rs2246154; hg19: chr20-1528038;