chr1-223259617-T-C

Variant names:

• chr1-223259617-T-C
• rs851195
• NM_017982.4:c.724+5013A>G

Variant summary

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

The NM_017982.4(SUSD4):​c.724+5013A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 152,224 control chromosomes in the GnomAD database, including 479 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 0.043 (479 hom., cov: 32)
• Consequence: SUSD4 NM_017982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017982.4. 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
	SUSD4	NM_017982.4	MANE Select	c.724+5013A>G		intron	N/A	NP_060452.3
	SUSD4	NM_001410929.1		c.940+5013A>G		intron	N/A	NP_001397858.1
	SUSD4	NM_001437664.1		c.724+5013A>G		intron	N/A	NP_001424593.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUSD4	ENST00000366878.9	TSL:1 MANE Select	c.724+5013A>G		intron	N/A	ENSP00000355843.4
	SUSD4	ENST00000608996.5	TSL:5	c.634+5013A>G		intron	N/A	ENSP00000477432.1
	SUSD4	ENST00000484758.6	TSL:2	c.511+5013A>G		intron	N/A	ENSP00000477374.1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6546 AN: 152106 Hom.: 472 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0432 AC: 6572 AN: 152224 Hom.: 479 Cov.: 32 AF XY: 0.0426 AC XY: 3174 AN XY: 74434

African (AFR) AF: 0.147 AC: 6107 AN: 41506

American (AMR) AF: 0.0205 AC: 314 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 68014

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0299 Hom.: 107

Bravo AF: 0.0497

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.64
PhyloP100		-0.22
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: rs851195; hg19: chr1-223432959;