rs2246154

Variant names:

• chr20-1547392-A-C
• rs2246154
• NM_178460.3:c.421+4299T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-1547392-A-C
• chr20-1547392-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000260861 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178460.3. 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
	SIRPD	NM_178460.3	MANE Select	c.421+4299T>G		intron	N/A	NP_848555.2	Q9H106
	SIRPD	NM_001410802.1		c.421+4299T>G		intron	N/A	NP_001397731.1	Q5TFQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIRPD	ENST00000381623.4	TSL:1 MANE Select	c.421+4299T>G		intron	N/A	ENSP00000371036.3	Q9H106
	SIRPD	ENST00000381621.5	TSL:3	c.421+4299T>G		intron	N/A	ENSP00000371034.1	Q5TFQ5
	ENSG00000260861	ENST00000566961.2	TSL:3	c.370-7057T>G		intron	N/A	ENSP00000457551.2	H3BUA5

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

African (AFR) AF: 0.925 AC: 38446 AN: 41556

American (AMR) AF: 0.735 AC: 11230 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3063 AN: 3470

East Asian (EAS) AF: 0.799 AC: 4140 AN: 5182

South Asian (SAS) AF: 0.842 AC: 4060 AN: 4824

European-Finnish (FIN) AF: 0.874 AC: 9259 AN: 10588

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57638 AN: 68006

Other (OTH) AF: 0.862 AC: 1819 AN: 2110

Alfa AF: 0.839 Hom.: 3371

Bravo AF: 0.851

Asia WGS AF: 0.835 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.54
PhyloP100		-0.95
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: rs2246154; hg19: chr20-1528038;