chr19-18431680-C-A

Variant names:

• chr19-18431680-C-A
• rs778835993
• NM_032627.5:c.469C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032627.5(SSBP4):​c.469C>A​(p.Arg157Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,552,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SSBP4 NM_032627.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 1 publications found

Genes affected

SSBP4 (HGNC:15676): (single stranded DNA binding protein 4) Predicted to enable single-stranded DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032627.5. 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
	SSBP4	NM_032627.5	MANE Select	c.469C>A	p.Arg157Arg	synonymous	Exon 7 of 18	NP_116016.1	Q9BWG4-1
	SSBP4	NM_001009998.4		c.403C>A	p.Arg135Arg	synonymous	Exon 6 of 17	NP_001009998.1	Q9BWG4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP4	ENST00000270061.12	TSL:1 MANE Select	c.469C>A	p.Arg157Arg	synonymous	Exon 7 of 18	ENSP00000270061.5	Q9BWG4-1
	SSBP4	ENST00000915352.1		c.403C>A	p.Arg135Arg	synonymous	Exon 6 of 17	ENSP00000585411.1
	SSBP4	ENST00000348495.10	TSL:2	c.403C>A	p.Arg135Arg	synonymous	Exon 6 of 17	ENSP00000252807.7	Q9BWG4-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000256 AC: 4 AN: 155998 AF XY: 0.0000238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1400550 Hom.: 0 Cov.: 33 AF XY: 0.00000289 AC XY: 2 AN XY: 691306

African (AFR) AF: 0.00 AC: 0 AN: 31762

American (AMR) AF: 0.000109 AC: 4 AN: 36778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 36096

South Asian (SAS) AF: 0.00 AC: 0 AN: 79696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080748

Other (OTH) AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		1.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs778835993; hg19: chr19-18542490;