chr7-141744038-G-A

Variant names:

• chr7-141744038-G-A
• rs6957284
• NM_003143.3:c.314+49G>A

Variant summary

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

The NM_003143.3(SSBP1):​c.314+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,522,404 control chromosomes in the GnomAD database, including 1,751 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 0.061 (964 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (787 hom.)
• Consequence: SSBP1 NM_003143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 4 publications found

Genes affected

SSBP1 (HGNC:11317): (single stranded DNA binding protein 1) SSBP1 is a housekeeping gene involved in mitochondrial biogenesis (Tiranti et al., 1995 [PubMed 7789991]). It is also a subunit of a single-stranded DNA (ssDNA)-binding complex involved in the maintenance of genome stability (Huang et al., 2009) [PubMed 19683501].[supplied by OMIM, Feb 2010]

SSBP1 Gene-Disease associations (from GenCC):

• optic atrophy 13 with retinal and foveal abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003143.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP1	NM_003143.3	MANE Select	c.314+49G>A		intron	N/A	NP_003134.1
	SSBP1	NM_001256510.1		c.314+49G>A		intron	N/A	NP_001243439.1
	SSBP1	NM_001256511.1		c.314+49G>A		intron	N/A	NP_001243440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP1	ENST00000265304.11	TSL:1 MANE Select	c.314+49G>A		intron	N/A	ENSP00000265304.6
	SSBP1	ENST00000481508.1	TSL:1	c.314+49G>A		intron	N/A	ENSP00000419665.1
	SSBP1	ENST00000498107.5	TSL:1	c.314+49G>A		intron	N/A	ENSP00000419541.1

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9231 AN: 152122 Hom.: 959 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0171 AC: 3754 AN: 219404 AF XY: 0.0124

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000455

Gnomad OTH exome AF: 0.00887

GnomAD4 exome AF: 0.00616 AC: 8438 AN: 1370166 Hom.: 787 Cov.: 20 AF XY: 0.00525 AC XY: 3592 AN XY: 684478

African (AFR) AF: 0.218 AC: 6728 AN: 30852

American (AMR) AF: 0.0120 AC: 473 AN: 39490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24146

East Asian (EAS) AF: 0.000332 AC: 13 AN: 39114

South Asian (SAS) AF: 0.000629 AC: 50 AN: 79468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49602

Middle Eastern (MID) AF: 0.00835 AC: 46 AN: 5512

European-Non Finnish (NFE) AF: 0.000286 AC: 299 AN: 1044848

Other (OTH) AF: 0.0145 AC: 829 AN: 57134

GnomAD4 genome AF: 0.0608 AC: 9262 AN: 152238 Hom.: 964 Cov.: 33 AF XY: 0.0588 AC XY: 4377 AN XY: 74454

African (AFR) AF: 0.211 AC: 8769 AN: 41492

American (AMR) AF: 0.0237 AC: 362 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68018

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0199 Hom.: 281

Bravo AF: 0.0706

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.68
PhyloP100		0.18
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: rs6957284; hg19: chr7-141443838;