4-56467946-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006947.4(SRP72):c.109+202C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,266 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (507 hom., cov: 32)
• Consequence: SRP72 NM_006947.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.992

Genes affected

SRP72 (HGNC:11303): (signal recognition particle 72) This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-56467946-C-G is Benign according to our data. Variant chr4-56467946-C-G is described in ClinVar as [Benign]. Clinvar id is 1181159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRP72	NM_006947.4	c.109+202C>G		intron_variant		ENST00000642900.1
SRP72	NM_001267722.2	c.109+202C>G		intron_variant
SRP72	XM_024454192.2	c.109+202C>G		intron_variant
SRP72	NR_151856.2	n.128+202C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRP72	ENST00000642900.1	c.109+202C>G		intron_variant			NM_006947.4	P1
SRP72	ENST00000510663.6	c.109+202C>G		intron_variant		1
SRP72	ENST00000504757.2	c.109+202C>G		intron_variant		2
SRP72	ENST00000505314.2	c.9+202C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11490 AN: 152146 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0754 AC: 11487 AN: 152266 Hom.: 507 Cov.: 32 AF XY: 0.0764 AC XY: 5691 AN XY: 74458

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.0655

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0300 Hom.: 18

Bravo AF: 0.0803

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs12505749; hg19: chr4-57334112;