rs1547789

Positions:

• chr1-223359323-G-A

Variant summary

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

The NM_017982.4(SUSD4):​c.148+3955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,010 control chromosomes in the GnomAD database, including 461 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 0.063 (461 hom., cov: 32)
• Consequence: SUSD4 NM_017982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

Genes affected

SUSD4 (HGNC:25470): (sushi domain containing 4) Involved in negative regulation of complement activation, alternative pathway and negative regulation of complement activation, classical pathway. Predicted to be located in extracellular region. Predicted to be integral component of membrane. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD4	NM_017982.4	c.148+3955C>T		intron_variant		ENST00000366878.9	NP_060452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD4	ENST00000366878.9	c.148+3955C>T		intron_variant		1	NM_017982.4	ENSP00000355843	P1

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9484 AN: 151892 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0528

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

GnomAD4 genome AF: 0.0625 AC: 9501 AN: 152010 Hom.: 461 Cov.: 32 AF XY: 0.0661 AC XY: 4908 AN XY: 74296

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0551

Alfa AF: 0.0561 Hom.: 54

Bravo AF: 0.0695

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.66

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: rs1547789; hg19: chr1-223532665;