chr1-223337035-C-A

Variant names:

• chr1-223337035-C-A
• rs17163819
• NM_017982.4:c.148+26243G>T

Variant summary

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

The NM_017982.4(SUSD4):​c.148+26243G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 152,312 control chromosomes in the GnomAD database, including 35 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 0.0073 (35 hom., cov: 32)
• Consequence: SUSD4 NM_017982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUSD4	NM_017982.4	c.148+26243G>T		intron_variant	Intron 2 of 8	ENST00000366878.9	NP_060452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUSD4	ENST00000366878.9	c.148+26243G>T		intron_variant	Intron 2 of 8	1	NM_017982.4	ENSP00000355843.4
SUSD4	ENST00000608996.5	c.58+26243G>T		intron_variant	Intron 1 of 7	5		ENSP00000477432.1
SUSD4	ENST00000484758.6	c.148+26243G>T		intron_variant	Intron 2 of 7	2		ENSP00000477374.1

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1103 AN: 152194 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00573

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

GnomAD4 genome AF: 0.00727 AC: 1107 AN: 152312 Hom.: 35 Cov.: 32 AF XY: 0.00820 AC XY: 611 AN XY: 74482

African (AFR) AF: 0.00217 AC: 90 AN: 41550

American (AMR) AF: 0.0164 AC: 251 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.106 AC: 547 AN: 5178

South Asian (SAS) AF: 0.0358 AC: 173 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68034

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00200 Hom.: 0

Bravo AF: 0.00836

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.81
PhyloP100		-0.087
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: rs17163819; hg19: chr1-223510377;