rs4822724

chr22-26484590-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001013694.3(SRRD):c.209+491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,036 control chromosomes in the GnomAD database, including 15,643 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 0.45 (15643 hom., cov: 32)
• Consequence: SRRD NM_001013694.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

Genes affected

SRRD (HGNC:33910): (SRR1 domain containing) Predicted to be involved in microtubule-based process; regulation of circadian rhythm; and regulation of heme biosynthetic process. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRRD	NM_001013694.3	c.209+491T>C		intron_variant		ENST00000215917.11
SRRD	XM_011530178.3	c.-51+491T>C		intron_variant
SRRD	XM_017028799.3	c.209+491T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRRD	ENST00000215917.11	c.209+491T>C		intron_variant		1	NM_001013694.3	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67767 AN: 151918 Hom.: 15645 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.446 AC: 67775 AN: 152036 Hom.: 15643 Cov.: 32 AF XY: 0.450 AC XY: 33437 AN XY: 74324

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.468

Alfa AF: 0.457 Hom.: 3882

Bravo AF: 0.430

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.5
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: rs4822724; hg19: chr22-26880556;