chr1-144963768-A-T

Variant names:

• chr1-144963768-A-T
• rs2790308
• NM_001271870.5:c.261-8167T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001271870.5(SRGAP2B):​c.261-8167T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
• Consequence: SRGAP2B NM_001271870.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 1 publications found

Genes affected

SRGAP2B (HGNC:35237): (SLIT-ROBO Rho GTPase activating protein 2B) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. This human-specific locus resulted from incomplete segmental duplication of the SLIT-ROBO Rho GTPase activating protein 2 locus. The encoded protein lacks the GTPase activating protein domain compared to proteins encoded by SLIT-ROBO Rho GTPase activating protein 2. The functionality of the protein encoded by this locus has been questioned, as several normal individuals with homozygous deletions for this locus have been identified, and the expression of this locus appears to be much lower than the similar SLIT-ROBO Rho GTPase activating protein 2C (SRGAP2C) locus. The SRGAP2C locus has been shown to encode a protein that functions antagonistically to SLIT-ROBO Rho GTPase activating protein 2 in cortical neuron development. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271870.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP2B	NM_001271870.5	MANE Select	c.261-8167T>A		intron	N/A	NP_001258799.2
	SRGAP2B	NM_001385226.1		c.261-3341T>A		intron	N/A	NP_001372155.1
	SRGAP2B	NM_001366280.2		c.261-8167T>A		intron	N/A	NP_001353209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP2B	ENST00000641863.3	MANE Select	c.261-8167T>A		intron	N/A	ENSP00000493121.1
	SRGAP2B	ENST00000612199.4	TSL:1	c.261-8167T>A		intron	N/A	ENSP00000477776.1
	SRGAP2B	ENST00000619678.2	TSL:5	n.261-3370T>A		intron	N/A	ENSP00000479960.2

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

Alfa AF: 0.280 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs2790308; hg19: chr1-144045339;