rs4895441

Variant names:

• chr6-135105435-A-G
• rs4895441

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -16 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Strong

The variant 6-135105435-A-G has been identified. The variant allele was found at a cumulative frequency of 0.213 (AC=32,424) in the gnomAD database across 152,152 control chromosomes, including 4,088 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.269. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Benign/Likely 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
• Publications: 131 publications found

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Benign. The variant received -16 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2688 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

 

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

There are no transcript annotations for this variant.

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.213	AC:32419	Hom:4086	AN:152034	Cov:32
GnomAD4 genome	AF: 0.213	AC:32424	Hom:4088	AN:152152	Cov:32
TOPMed (Bravo)	AF: 0.200	AC:53014	Hom:6250	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.252	AC:187207	Hom:24788	AN:744124	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.211	AC:494	Hom:63	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.305	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.243	AC:73	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.166	AC:576	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.352	AC:2549	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.142	AC:25	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.367	AC:44964	Hom:8250	AN:122674	Cov:
Turkish Variome	AF: 0.243	AC:375	Hom:44	AN:1546	Cov:
UK10K	AF: 0.270	AC:2042	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.282	AC:2524	Hom:384	AN:8960	Cov:

Showing 14 sources

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.4
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.64
GPN-Star LLR	N/A	-0.048
GPN-Star score	N/A	0.048
PhyloP100	Benign	0.39

Showing 7 of 7 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs4895441;

hg19: chr6-135426573;

COSMIC: COSV73231475;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar