rs4895441

Variant names:

• chr6-135105435-A-G
• rs4895441

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.213 in 152,152 control chromosomes in the GnomAD database, including 4,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.21 (4088 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.391

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-135105435-A-G is Benign according to our data. Variant chr6-135105435-A-G is described in ClinVar as [Benign]. Clinvar id is 132871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32419 AN: 152034 Hom.: 4086 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.213 AC: 32424 AN: 152152 Hom.: 4088 Cov.: 32 AF XY: 0.213 AC XY: 15855 AN XY: 74376

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.190

Alfa AF: 0.257 Hom.: 11503

Bravo AF: 0.200

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 28, 2020

H3Africa Consortium

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.083, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4895441; hg19: chr6-135426573; COSMIC: COSV73231475;