Genetic Variant SIRPD:c.422-144C>T (chr20-1537454-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178460.3(SIRPD):c.422-144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 975,380 control chromosomes in the GnomAD database, including 20,136 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 0.18 ( 2919 hom., cov: 32)

Exomes 𝑓: 0.19 ( 17217 hom. )

Consequence

SIRPD
NM_178460.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.154

Publications

9 publications found

Variant links:

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]

SIRPD links:

ENSG00000242324 (HGNC:):

ENSG00000242324 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 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.422-144C>T		intron	N/A	NP_848555.2	Q9H106
	SIRPD	NM_001410802.1		c.422-141C>T		intron	N/A	NP_001397731.1	Q5TFQ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIRPD	ENST00000381623.4	TSL:1 MANE Select	c.422-144C>T	intron	N/A	ENSP00000371036.3	Q9H106
SIRPD	ENST00000381621.5	TSL:3	c.422-141C>T	intron	N/A	ENSP00000371034.1	Q5TFQ5
SIRPD	ENST00000429387.5	TSL:3	c.68-144C>T	intron	N/A	ENSP00000410072.1	H0Y747

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28112

AN:

152092

Hom.:

2919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.194

AC:

159492

AN:

823170

Hom.:

17217

AF XY:

0.193

AC XY:

80087

AN XY:

414658

show subpopulations

African (AFR)

AF:

0.131

AC:

2619

AN:

19978

American (AMR)

AF:

0.135

AC:

2789

AN:

20598

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

4546

AN:

15738

East Asian (EAS)

AF:

0.000393

AC:

AN:

33038

South Asian (SAS)

AF:

0.144

AC:

8018

AN:

55676

European-Finnish (FIN)

AF:

0.265

AC:

9192

AN:

34650

Middle Eastern (MID)

AF:

0.267

AC:

1057

AN:

3956

European-Non Finnish (NFE)

AF:

0.206

AC:

123874

AN:

601416

Other (OTH)

AF:

0.194

AC:

7384

AN:

38120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5789

11577

17366

23154

28943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3332

6664

9996

13328

16660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.185

AC:

28127

AN:

152210

Hom.:

2919

Cov.:

AF XY:

0.183

AC XY:

13657

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.132

AC:

5497

AN:

41552

American (AMR)

AF:

0.146

AC:

2235

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

992

AN:

3470

East Asian (EAS)

AF:

0.00251

AC:

AN:

5182

South Asian (SAS)

AF:

0.136

AC:

658

AN:

4830

European-Finnish (FIN)

AF:

0.280

AC:

2965

AN:

10584

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15144

AN:

67984

Other (OTH)

AF:

0.204

AC:

430

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1156

2312

3469

4625

5781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.211

Hom.:

1795

Bravo

AF:

0.173

Asia WGS

AF:

0.0800

AC:

280

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.5

(source)

DANN

Benign

0.73

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over