chr11-65579427-C-G

Variant names:

• chr11-65579427-C-G
• rs369857321
• NM_001099409.3:c.249C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001099409.3(EHBP1L1):​c.249C>G​(p.Thr83Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000641 in 1,543,936 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00067 (2 hom.)
• Consequence: EHBP1L1 NM_001099409.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81
• Publications: 1 publications found

Genes affected

EHBP1L1 (HGNC:30682): (EH domain binding protein 1 like 1) Predicted to be involved in actin cytoskeleton organization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-65579427-C-G is Benign according to our data. Variant chr11-65579427-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099409.3. 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
	EHBP1L1	NM_001099409.3	MANE Select	c.249C>G	p.Thr83Thr	synonymous	Exon 3 of 19	NP_001092879.1	Q8N3D4
	EHBP1L1	NM_001351087.2		c.249C>G	p.Thr83Thr	synonymous	Exon 3 of 18	NP_001338016.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1L1	ENST00000309295.9	TSL:1 MANE Select	c.249C>G	p.Thr83Thr	synonymous	Exon 3 of 19	ENSP00000312671.4	Q8N3D4
	EHBP1L1	ENST00000968317.1		c.249C>G	p.Thr83Thr	synonymous	Exon 3 of 20	ENSP00000638376.1
	EHBP1L1	ENST00000968331.1		c.249C>G	p.Thr83Thr	synonymous	Exon 3 of 18	ENSP00000638390.1

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 64 AN: 151962 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000463 AC: 74 AN: 159832 AF XY: 0.000624

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000212

Gnomad ASJ exome AF: 0.000906

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000787

Gnomad OTH exome AF: 0.000477

GnomAD4 exome AF: 0.000665 AC: 926 AN: 1391856 Hom.: 2 Cov.: 32 AF XY: 0.000669 AC XY: 459 AN XY: 685640

African (AFR) AF: 0.000125 AC: 4 AN: 31930

American (AMR) AF: 0.000257 AC: 9 AN: 35052

Ashkenazi Jewish (ASJ) AF: 0.000554 AC: 13 AN: 23450

East Asian (EAS) AF: 0.00 AC: 0 AN: 37584

South Asian (SAS) AF: 0.000367 AC: 28 AN: 76324

European-Finnish (FIN) AF: 0.000142 AC: 7 AN: 49378

Middle Eastern (MID) AF: 0.00287 AC: 16 AN: 5570

European-Non Finnish (NFE) AF: 0.000757 AC: 814 AN: 1074854

Other (OTH) AF: 0.000606 AC: 35 AN: 57714

GnomAD4 genome AF: 0.000421 AC: 64 AN: 152080 Hom.: 0 Cov.: 30 AF XY: 0.000363 AC XY: 27 AN XY: 74322

African (AFR) AF: 0.000169 AC: 7 AN: 41440

American (AMR) AF: 0.000262 AC: 4 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000757 Hom.: 0

Bravo AF: 0.000638

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.61
PhyloP100		-1.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs369857321; hg19: chr11-65346898;