chr7-56071812-A-T

Variant names:

• chr7-56071812-A-T
• rs7806994
• NM_015411.4:c.225-1185A>T

Variant summary

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

The NM_001366648.2(SUMF2):​c.225-1185A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 149,646 control chromosomes in the GnomAD database, including 2,135 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 0.16 (2135 hom., cov: 30)
• Consequence: SUMF2 NM_001366648.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 7 publications found

Genes affected

SUMF2 (HGNC:20415): (sulfatase modifying factor 2) The catalytic sites of sulfatases are only active if they contain a unique amino acid, C-alpha-formylglycine (FGly). The FGly residue is posttranslationally generated from a cysteine by enzymes with FGly-generating activity. The gene described in this record is a member of the sulfatase-modifying factor family and encodes a protein with a DUF323 domain that localizes to the lumen of the endoplasmic reticulum. This protein has low levels of FGly-generating activity but can heterodimerize with another family member - a protein with high levels of FGly-generating activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366648.2. 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
	SUMF2	NM_015411.4	MANE Select	c.225-1185A>T		intron	N/A	NP_056226.3
	SUMF2	NM_001366648.2		c.225-1185A>T		intron	N/A	NP_001353577.1
	SUMF2	NM_001130069.4		c.225-1185A>T		intron	N/A	NP_001123541.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF2	ENST00000434526.8	TSL:1 MANE Select	c.225-1185A>T		intron	N/A	ENSP00000400922.3
	SUMF2	ENST00000342190.11	TSL:1	c.225-1185A>T		intron	N/A	ENSP00000341938.7
	SUMF2	ENST00000395436.7	TSL:1	c.225-1185A>T		intron	N/A	ENSP00000378824.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24575 AN: 149528 Hom.: 2129 Cov.: 30

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.164 AC: 24603 AN: 149646 Hom.: 2135 Cov.: 30 AF XY: 0.162 AC XY: 11860 AN XY: 73018

African (AFR) AF: 0.159 AC: 6453 AN: 40636

American (AMR) AF: 0.125 AC: 1878 AN: 14976

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 553 AN: 3456

East Asian (EAS) AF: 0.0119 AC: 60 AN: 5030

South Asian (SAS) AF: 0.108 AC: 513 AN: 4754

European-Finnish (FIN) AF: 0.183 AC: 1820 AN: 9944

Middle Eastern (MID) AF: 0.170 AC: 48 AN: 282

European-Non Finnish (NFE) AF: 0.189 AC: 12749 AN: 67600

Other (OTH) AF: 0.141 AC: 291 AN: 2070

Alfa AF: 0.178 Hom.: 262

Bravo AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.80
DANN	Benign	0.12
PhyloP100		-3.4
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: rs7806994; hg19: chr7-56139505;