rs4895441

Positions:

• chr6-135105435-A-G

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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Benign, criteria provided, single submitter	research	H3Africa Consortium	Oct 28, 2020	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. -
Benign, criteria provided, single submitter	clinical testing	Genomic Research Center, Shahid Beheshti University of Medical Sciences	May 03, 2020	- -

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;