4-88121700-GA-TG

Variant names:

• chr4-88121700-GA-TG
• NM_004827.3:c.623_624delTCinsCA
• ABCG2 p.Phe208Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004827.3(ABCG2):​c.623_624delTCinsCA​(p.Phe208Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCG2 NM_004827.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.98
• Publications: 0 publications found

Genes affected

ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004827.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_004827.3	MANE Select	c.623_624delTCinsCA	p.Phe208Ser	missense	N/A	NP_004818.2	Q9UNQ0-1
	ABCG2	NM_001348985.1		c.623_624delTCinsCA	p.Phe208Ser	missense	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001348986.2		c.623_624delTCinsCA	p.Phe208Ser	missense	N/A	NP_001335915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.623_624delTCinsCA	p.Phe208Ser	missense	N/A	ENSP00000237612.3	Q9UNQ0-1
	ABCG2	ENST00000515655.5	TSL:1	c.623_624delTCinsCA	p.Phe208Ser	missense	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000889086.1		c.623_624delTCinsCA	p.Phe208Ser	missense	N/A	ENSP00000559145.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

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.

Other links and lift over

hg19: chr4-89042852;